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7 


MODERN  CLINICAL   MEDICINE 

DISEASES   OE    METABOLISM 
AND   OE   THE    BLOOD 

ANIMAL  PARASITES 

TOXICOLOGY 

EDITED   BY 

RICHARD    C.    CABOT,    M.I). 

INSTRUCTOR  IN  CLINICAL   MEDICINE   IN  THE   MEDICAL  SCHOOL  OF   HARVARD   INIYKHSITY 


AN   AUTHORIZED  TRANSLATION   FROM   "DIE  DEUTSCHE   KLINIK - 
UNDER  THE  GENERAL  EDITORIAL  SUPERVISION  OF 

JULIUS     L.    SALINGER,    M.I). 


WITH  ONE  COLORED   PLATE  ASK   FIFTY-EIGHT 
ILLUSTRATIONS   TN    THE   TEXT 


9  W, 


NEW     YORK     AND    LONDON 

D.     A  PPL  ETO  N     AND     COM  P  A  \  Y 

1906 


27 


Copyright,  1006,  by 
D.   APPLETON   AND   COMPANY 


C 


PRINTED   AT   THE   APPLETON    PRESS 
NEW    YORK,    U.    S.    A. 


INTRODUCTION 


Although  the  statement  of  Prof.  Hoppe-Seyler  that  "The  process  of 
life  of  the  organism  ls,  in  the  main,  a  complete  mystery"  is  still  true, 
much  has  been  accomplished  by  the  researches  of  modern  physiologists  and 
clinicians  who  have  endeavored  to  find  the  key  to  this  enigma.  Perhaps  in 
no  realm  of  medicine  has  labor  fructified  so  richly  as  in  the  recent  study 
of  metabolism.  This  has  been  of  value  not  only  in  diagnosis  hut.  even  more 
so.  from  the  standpoinl  of  treatment.  It  may  he  confidently  stated  thai  the 
treatment  of  some  diseases  of  metabolism,  such  as  diabetes  mellitus,  gout, 
and  obesity,  now  rests  on  a  scientific  basis.  This  advance  is  almost  exclu- 
sively «lue  to  the  labors  of  the  modern  German  school  of  physiologists  and 
internal  clinicians. 

What  is  true  of  the  pathology  of  metabolism  may  also  be  asserted  of 
diseases  of  the  blood.  The  study  of  maladies  whose  etiology  and  pathology 
were  formerly  obscure  has  now  been  simplified,  their  relations  classified,  and 
the  whole  arranged  in  exacl  scientific  order.  The  processes  of  blood  forma- 
tion and  blood  degeneration,  while  not  yei  forming  an  open  hook,  have  in 
pari  been  clearly  portrayed.  That  therapy  has  not  kepi  pace  with  this  ad- 
vance affords  an  opportunity  tor  the  physician  of  the  twentieth  century, 
hut  much  has  already  been  accomplished,  and  many  problems  have  been 
Bolved.  for  this  progress  also  the  medical  world  is  indebted  t<»  modern 
research. 

The  object  of  this  volume  is  to  present  a  picture  of  ,]!.., •;!-<•-  which  were 
formerly  designated  as  of  "obscure  causation/5  and  to  outline  their  treat- 
ment.    Each  article  is  the  work  of  a  master  in  his  special  ßeld  of  labor. 

In  the  translation  an  endeavor  ha-  I n   made  to  adhere  a-  closely  as 

possible  to  the  individual  style  of  each  contributor  without  the  subserviency 
of  clearness  in  the  text. 

in 


IV  INTRODUCTION 

I  am  indebted  for  much  valuable  service  in  the  preparation  of  this  volume 
to  my  secretary.  Miss  M.  A.  Clarke. 

In  anticipation  of  the  fact  that  many  points  in  regard  to  these  affec- 
tions will  be  searched  for  by  the  reader,  and  to  facilitate  this,  an  endeavor 
has  been  made  to  add  a  comprehensive  and  full  general  index. 

Julius  L.  Salinger. 
1729  North  42xd  Street,  Philadelphia. 


EDITOR'S   PREFACE 


We  have  in  English  no  discussion  of  the  Constitutional  Diseases  which 
treats  with  any  fulness  the  problems  arising  when  we  consider  the  reasons  for 
what  occurs  in  these  diseases. 

The  rationale  of  the  symptomatology,  the  rationale  of  treatment  (i.e., 
in  diabetes)  is  here  admirably  set  forth  by  clinicians  each  of  whom  speaks 
with  authority. 

The  writers  have  wisely  confined  themselves  for  the  most  pari  to  thorough 
discussions  of  certain  points  in  each  of  the  diseases  considered — making  no 
fatuous  attempt  to  compress  a  huge  subject  into  narrow  limits.  They  have 
brought  their  subjects  up  to  date  and  given  very  frankly  their  persona]  views 
on  the  points  at   issue. 

For  the  manner  and  for  the  matter  of  their  work.  therefore3  we  are  in- 
debted to  our  Teutonic  brethren,  and  we  arc'  glad  thai  the  honk  will  now  find 
a  Large  circle  of  readers. 

Richard  C.  Cabot. 

190  Maklhokoi/ch  Strkkt,    Boston,    Mass. 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/diseasesofmetaboOOcabo 


LIST   OF   CONTRIBUTIONS 


The   Quantitative   Analysis   of  Disturbances   of  Metabolism    in    the   Clinic 

By  \V.  Weintbaud,  Wiesbaden. 
Over-nutrition  and  Under-nutrition.    By  ('.  v.  Noobden,  Frankfort-on-Main. 
Diabetes  Mellitus.     By  B.  Xatxyn,  Strassburg. 
Diabetes  Insipidus.     By  D.  Gehiiardt,  Strassburg. 
(luiil.     By  \V.  Ebstein,  <;<">ttingen. 
Obesity.     By  \V.  Ebstein,  Göttingen. 

Myxedema    with    Special   Reference   to   Organotherapy.     By   C.    A.    Ewald, 

Berlin. 

Addison's  Disease.     By  L.  Reiss,  Berlin. 

Acromegalia.     By  C.  Bexda,  Berlin. 

Chronic  Articular  Rheumatism.     By  W.  1 1  is.  Basel. 

Pentosuria.     By  F.  Blumenthal,  Berlin. 

Blood  inn/  Blood  Examination.     By  A.  Lazabus,  Charlottenburg  (  Berlin). 

The  Anemias.     By  I'.  Ehelich,  Frankfort-on-Main,  and  A.  Lazabus,  Char- 

Lottenburg  (  Berlin ). 
Chlorosis.     By  E.  Gbawitz,  Charlottenburg  (Berlin). 
Leukemia.     By  W.  von  Lei  be,  Würzburg. 

Pseudo-leukemia  (Hodgkin's  Disease  and  BanWs  Disease).    By  II.  Senatob, 
Berlin. 

77/r  Hemorrhagic  Diatheses.     By  M.  Litten,  Berlin. 
77m'  Animal  Parasites  of  Man.     By  E.  Peipeb,  Greifswald. 
Important  Poisons  "nil  Their  Treatment.     By  EL  v.  Jaksoh,  Prague. 

vii 


CONTENTS 


PAGE 

The  Quantitative  Analysis  of  Disturbances  of  Metabolism  ix  the  Clinic    .  1 

Introduction 1 

Consumption  of  Food  in  the  Healthy 4 

A.  The  Laws  of  Nutrition 4 

Energy  .Metabolism  per  Square  Meter  of  Body  Surface         ...  5 

B.  The  Methods  for  Estimating  the  Calory  Requirement  of  the  Body    .  6 

C.  The  Energy  Requirement  of  the  Healthy 9 

D.  The  Albumin  Minimum 13 

E.  The  Requirements  for  Albumin  Deposition 15 

The  Food  Requirement  of  the  Sick 21 

The  Degree  of  Oxidation 22 

The  Maintenance  Diet  and  the  Proteid  Requirement  of  the  Sick    ...  37 

Disturbances  in  the  Absorption  of  Food !•"> 

Concluding  Remarks 49 

Over-Nitrition  and  Under-Nutritiox 54 

1.  Conception  of  the  "Condition  of  Nutrition" 54 

2.  Increase  of  Flesh  and  Increase  of  Fat 55 

3.  Occurrence  and  Consequences  of  Under-Nutrition 59 

4.  Occurrence  and  Consequences  <>i'  Over-Nutrition <>1 

5.  Indications  for  Hypernutrition  and  Hyponutrition (V2 

A.  Over-Nutrition 63 

B.  Under-Nutrition r>7 

G.  Remarks  Regarding  the  Technic  of  Over-Nutrition  and  Under-Nutrition    .  ('>'.) 

A.  The  Technic  of  Forced  Feeding 70 

B.  The  Technic  of  Antifal  Cures 72 

1  )l  \i:i:i  BS    Ml  LLITUS 77 

1.  Glycosuria  and  Diabetes 77 

11.    The  Various  bonus  of  Diabetes;  Diabetic  Predisposition     ....  80 

III.  Mild  and  Severe  Forms  of  Diabetes;  Course,  Symptomatology  and  Com- 

plications    83 

IV.  The  Theory  of  the  Treatment  of  Diabetes s7 

V.  Practical  Therapy 92 

\  1.  Tables 103 

Short   Popular  Dietetic  bulcs  im-  Diabetics ion 

ix 


X  CONTEXTS 

PAGE 

Diabetes  Insipidus 110 

Symptoms  and  Clinical  Course 112 

Diagnosis 121 

Treatment 122 

Gout 125 

The  Pathogenesis  of  Gout .        .        .        .126 

Symptomatology 132 

Course  and  Prognosis 145 

Diagnosis 146 

Treatment 146 

Obesity 151 

Etiology 133 

Symptomatology 155 

Diagnosis 159 

Treatment 160 

Myxedema  with  Special  Reference  to  Organotherapy 179 

History 179 

Etiology 180 

Symptoms 180 

Pathology 186 

Therapy 188 

Addison's  Disease 199 

Clinical  Picture  of  Addison's  Disease 200 

Grosser  Pathologico- Anatomical  Lesions  in  Addison's  Disease 202 

Anatomy  and  Physiology  of  the  Adrenals 204 

Pathologico-Anatomical  Changes  of  the  Nervous  System  in  Addison's  Disease  215 

Diagnosis 222 

Therapy 223 

Acromegalia 229 

Etiology 230 

Symptoms 231 

Pathology 234 

Pathological  Anatomy 237 

Treatment 242 

Chronic  Articular  Rheumatism 243 

Pathology 248 

Clinical  Symptoms 250 

Treatment 257 

Literature 259 

Pentosuria 262 

Blood  and  Blood  Examination 275 

I.  Hemoglobin 277 

II.  Counting  the  Blood-Corpuscles 281 


CONTEXTS  XI 

PAGE 

III.  Counting  the  Leukocytes 283 

IV.  Specific  Gravity 2S4 

V.  Alkalinity 286 

VI.  Volume  of  Red  Cells 287 

VII.  Spectroscopic  Examination 287 

VIII.  Agglutinative  Reactions 288 

IX.  Bacteriological  Examination 290 

The  Anemias 304 

Simple  Anemia 305 

Progressive  Pernicious  Anemia 310 

The  Course  of  the  Disease 317 

Therapy 318 

Chlorosis 320 

Symptoms 320 

The  Blood 325 

Pathological  Anatomy 329 

Frequency  of  Chlorosis  with  Regard  to  Sex,  Age  and  Locality      ....  330 

Predisposing  Influences 331 

The  Genesis  of  Chlorosis 333 

Diagnosis 336 

Course  of  the  Disease 337 

Prognosis 339 

Treatment 339 

Prophylaxis 343 

Leukemia 344 

Composition  of  the  Blood 344 

Symptoms  and  Brood-Changes 34S 

Diagnosis 364 

Leukocytosis 364 

Prognosis 367 

Treatmenl 367 

Pbei  do-Lei  kemia  (Hodgkin'b  Disease  \m>  Banti'b  Disease) 370 

Hodgkin's  Disease 371 

Diagnosis '■''''• 

Etiology 377 

Course,  Duration  and  Result "7s 

Therapy 378 

Bant  is  Disease 

The  Hemorrhagic  Diatheses :;ss 

Scurvy 388 

History 

Etiology 

Pathological  Anatomy 399 


xii  CONTENTS 

TAGE 

Symptomatology 401 

Diagnosis 409 

Prognosis 410 

Prophylaxis  and  Treatment  ...........  410 

Hemophilia   (Bleeder's  Disease)  ..........  413 

Pathological  Anatomy 430 

Symptomatology  and  Course 434 

Local  Hemorrhages  upon  a  Hemophilic  Basis 442 

Prognosis 451 

Treatment 452 

Morbus  Maculosus  Werlhofii  (Purpura) 

(Purpura  Simplex,   Hemorrhagica,   Rheumatica  seu  Peliosis,  Rheumatica 

Schoenleinii) 457 

Definition 457 

Etiology 458 

General  Clinical  Picture 469 

Pathological  Anatomy 487 

Special  Symptomatology 490 

Treatment 496 

The  Animal  Parasites  of  Man 501 

Protozoa 505 

Trematodes 508 

Cestodes 514 

Prognosis 524 

Therapy 525 

Echinococcus  Disease 526 

Symptoms 532 

Treatment 533 

Echinococci  of  Various  Organs 53 1^ 

Nematoda,  Thread-Worms 544 

Ankylostomiasis — Uncinariasis 560 

Arthropoda 565 

Fly  Larva'   (Maggots) 573 

Important  Poisons  and  Their  Treatment 579 


LIST   OF  ILLUSTRATIONS 


FIG. 
I. 


3. 

4. 

5. 
6. 

7. 

8. 

9. 
10. 
11. 
12- 
14. 
1.-.. 
Ki. 
17. 
is. 
1«.). 
20. 
21. 
22. 
23. 
24. 
26. 
•je. 

2'.). 

30 
.31. 
32. 
33. 
34. 

36. 


Incipient  Myxedema 

Advanced  .Myxedema 

.Myxedema  in   the  stage  of  recovery 

Röntgen  picture  showing  Heberden's  nodes 

Metatarso-phalangeaJ  articulation  with  beginning  chronic  arthritis 
Subcutaneous  nodules  upon  dorsal  tendon  sheaths  in  chronic  exudati 

thritis 

Patellar   cartilage   after   an    attack    of  gout 

Radiograph  of  hand  of  a  gouty  patient     .... 

Hemometer.     (After  v.   Fleischl-Miescher) 

Hemometer.     (After  Sahli) 

Hemometer.     (After  Sahli) 

13.    Hemophoto<>;raph.      (After  Gaertner)      .... 

Bemocytometer.     (After  Thoma) 

Microscopic   picture  with   blood-corpuscles.      (After   Landois) 
Absorption  spectra  of  hemoglobin.     (After  Landois) 
Relapsing  Fever  spirilli.     (After  v.  Jaksch) 

Im-   of   forceps   in    blood   examination  .... 

Small   copper   kettle    for   staining   solutions 

Ehrlich's   eve-piece    with    in,-   diaphragm        .... 

of  Hodgkin's  disease 

<  lenealogical  tree  of  the  bleeder  family  Mam  pel.     (Aftei  Lo 
Genealogical    tree  of  a  hleeder  family.     (After  II.  Gocht) 

llogica]  tree  of  a  family  showing  Daltonism.      (After  Hon 
Genealogical  tree  of  a  bemeralopic  family.     (After  I'..  Ammann) 
28.  Leydenia  Gemmipara,     (After  von  Leyden-Schaudinn) 
Trichomonas  Vaginalis.  (After  Künstler)    .... 
Balantidium  Minutum.     (After  Schaudinn) 
Nyctotherus  Faba.     (After  Schaudinn)      .... 

Distomum    Hepaticum,    I.inne 

Distomum  Westermanni  and  ovum.     (After  Katsurada) 

Distomum   Spathulatum   and   ovum.      (After    Katsurada) 

Ova  of  Distomum   Haematobium 

<  >va   of  Tenia   Solium 


e  polyar- 


XIV  LIST  OF   ILLUSTRATIONS 

FIG.  PAGE 

37.  Ova  of  Tenia  Saginata 515 

38-42.  Tenia  Confusa,  Ward.     (After  Guyer) 517 

43.  Tenia  Africana.     (After  v.  Linstow) 51S 

44.  Tenia  Asiatica.     (After  v.  Linstow) 519 

45.  Cercocyst  from  Cyprinotus  Incongruens,  1900 519 

46.  Hymenolepis  Lanceolata,  Bloch 520 

47.  Head  of  Hymenolepis  Lanceolata,  greatly  enlarged 520 

48.  Proglottid  of  Hymenolepis •  520 

49.  Bothriocephalus  Grandis.     Proglottid  and  ovum.     (After  Ijima  and  Kurimoto)  521 

50.  Tenia  Echinococcus 527 

51.  Head  of  Tenia  Echinococcus 527 

52.  Expectorated  Echinococcus  membrane 538 

53.  Filaria  Embryos 547 

54.  Ankylostoma  Duodenale 561 

55.  Ova  of  Ankylostoma  Duodenale 561 

56.  Larva  of  Ankylostoma  Duodenale 561 

57-58.  Sarcopsylla  Penetrans,  Sand-flea 573 


COLORED  PLATE 
Blood  Cells Facing     302 


DISEASES    OF    METABOLISM 


THE    QUANTITATIVE    ANALYSIS 

OF    DISTURBANCES    OF    METABOLISM 

IN    THE    CLINIC 

By  W.   WEINTRAUD,  Wiesbaden 

Contents:  Introduction. — Xormal  metabolism :  A.  The  laws  of  nutrition; 
B.  The  methods  for  estimating  the  calory  requirement  of  man;  C.  The 
normal  energy  requirement;  D.  The  albumin  minimum;  E.  The  require- 
ments for  storing  up  albumin. — The  food  requirement  of  the  sich:  The 
degree  of  oxidation;  maintenance  diet  and  albumin  requirement;  dis- 
turbances of  absorption  of  food. — Concluding  remarks. 

INTRODUCTION 

During  the  past  decade  the  scientific  researches  of  internal  medicine  have 
been  made  chiefly  in  the  clinico-chemical  laboratory. 

Prepared  and  developed  by  physiology,  the  pathology  of  metabolism  offered 
a  fruitful  field  for  study,  hence  it  was  not  surprising  that  numerous  young 
investigators  soon  found  here  their  sphere  of  activity.  A  flood  of  researches 
in  metabolism  was  the  result.  Clinical  literature  of  the  latest  epoch  bears 
the  lasting  impress  of  these  workers.  Many  interesting  questions  concerning 
the  laws  of  metabolism  can  be  regarded  as  decided,  chiefly  by  tin'  theoretic 
conclusions  based  on  these  clinical  studies,  but  an  eminently  practical  issue 
has  also  been  attained:  Based  upon  these  fundamental  laws,  a  rational  therapy 
of  nutrition  bus  been  evolved  which  affords  an  extraordinarily  fruitful  field 
for  professional  usefulness. 

It  i-  interesting  to  recount.  /'//  extenso,  the  valuable  discoveries  which  have 
come  from  the  clinico-chemical  laboratories,  and  have  brilliantly  justified 
their  raison  d'etre. 

'The  problems  which  arose  for  solution,  as  ><><>n  as  investigation  passed 

beyond  the  mere  examination  of  urine  for  albumin  and  sugar,  were  manifold. 
often  they  led  into  the  realm  of  physiology,  and  thus  it  happened  that  many 
obscure  point-  in  the  physiology  of  digestion  and  metabolism  were  brilliantly 
illuminated  by  the  labors  of  clinicians,  and  experimental  investigation  in  the 
clinical  laboratory  ha-  (specially  enriched  our  knowledge  of  the  physiology  of 
metabolism. 

With  energy  ami  thoroughness,  therefore,  researches  into  the  pathology  of 
metabolism  were  pursued  clinically.  The  wards  of  the  hospitals  offered  rich 
material  and  abundant  opportunity  for  observing  the  course  of  metabolic 
processes  under  abnormal  conditions,  and  the  de-ire  to  study  physiological 
<pie>tions  at  the  bedside  was  a-  much  promoted  by  stimulus  from  the  phj 
logic  laboratories  of   Hoppe-Seyler,   Ludwig.  Voit,    Pfiuger,  Salkowski,  and 

l 


2  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

Baumann  as  by  the  desire  to  find  a  key  to  the  comprehension  of  pathologic 
processes. 

The  practical  result  of  these  labors  may  be  noted  in  the  extraordinary 
interest  manifested  everywhere  to-day  in  modern  dietotherapy.  For  this  rea- 
son it  is  worth  while  to  cast  a  retrospective  glance  over  the  long  road  which  has 
led  to  this  satisfactory  result. 

The  scientific  study  of  metabolism  began  when  Lavoisier,  in  1780,  desig- 
nated chemical  processes  in  the  animal  economy  as  the  source  of  heat  accom- 
panying all  processes  of  life.  He  taught  us  that  the  food  products  in  the 
body  utilized  the  oxygen  breathed  in  with  the  inspired  air  and  decomposed, 
producing  carbonic  acid;  that  this  process  is  therefore  analogous  to  the 
combustion  of  organic  substances  outside  of  the  body,  and  is  an  oxidation 
process  which  is  the  most  important  source  of  animal  heat. 

A  long  time  elapsed  before  the  discovery  of  the  law  of  conservation  of 
energy  also  permitted  new  conceptions  in  the  realm  of  biology  (R.  Meyer).  In 
opposition  to  the  view  that,  besides  combustion,  still  other  independent  sources 
of  heat  were  present  in  the  circulation  of  the  blood  (friction,  etc.),  the  opin- 
ion became  general  that  all  expressions  of  force  which  are  recognized  in  the 
living  organism  (i.  e.,  production  of  heat  and  capacity  for  work)  were  sus- 
ceptible of  a  uniform  explanation.  They  originate  from  the  energy  which  is 
furnished  the  body  by  the  food.  By  tireless  and  long-continued  original 
researches,  Rubner  proved  conclusively  that  the  law  of  the  conservation  of 
energy,  the  correctness  of  which  R.  Meyer  and  Helmholtz  proved  in  the  realm 
of  physics,  deserves  proper  recognition  also  in  biology.  The  supply  of  energy 
contained  in  the  food  passes  through  the  animal  body  without  diminution. 

Thus  the  law  of  the  permutation  of  forces,  which  had  its  origin  in  Lavoi- 
sier's discovery  of  combustion  as  the  source  of  energy  for  the  organism,  was 
conclusively  demonstrated  by  Rubner. 

It  was  an  important  epoch  in  the  development  of  the  laws  of  metabolism 
when  Justus  von  Liebig  demonstrated  the  identity  of  the  proteids  of  the  ani- 
mal and  vegetable  organisms  in  their  chemical  properties,  and  explained  the 
relations  of  the  albumin  products  of  the  food  to  the  nitrogenous  products  of 
decomposition  in  the  urine.  We  owe  to  him  the  knowledge  that  it  is  albumin, 
fat,  and  carbohydrates  which  are  the  basis  of  metabolic  processes.  He  was 
the  first  to  emphasize  the  fact  of  the  unequal  importance  of  the  products  neces- 
sary for  structural  formation  in  the  animal  organism.  He  assumed  that  the 
albumin  introduced  with  the  food  alone  reconstructs  that  which  has  been 
destroyed  by  the  activity  of  the  body,  and  called  albumin  the  plastic  (tissue- 
forming)  food  product,  contrasting  with  it  the  N-free  products  (fat  and 
carbohydrates)  as  respiratory  products.  These  alone,  he  supposed,  were 
attacked  directly  by  the  oxygen  in  the  air,  and  by  their  combustion  protected 
the  plastic  products,  the  albumin,  from  oxidation. 

But  this  theory  of  a  division  of  all  food  products  into  two  opposite  groups 
could  not  be  maintained,  and  the  theory  of  Liebig  that  the  oxygen  taken  up 
in  respiration  caused  the  disintegration  of  the  food  products,  and  that  its 
amount  decided  the  degree  of  metabolism  was  also  later  proven  to  be  unten- 


INTRODUCTION  3 

able.  We  know  to-day  that  the  causal  relation  between  oxygen  intake  and 
food  consumption  as  accepted  by  Liebig  does  not  exist,  but  that  in  the  living 
protoplasm  of  tlte  cell  exists  the  cause  of  the  decomposition  going  on  in  the 
organism. 

Food  decomposition  does  not  take  place  in  the  Mood  and  fluids,  as  was 
assumed  at  that  time,  but  in  the  tissues,  where  the  decomposition  is  produced 
by  the  chemical  activity  of  the  cell.-.1 

The  type  and  rate  of  metabolism  are  determined  neither  by  the  presence 
nor  by  the  absence  of  oxygen,  but  only  the  energies  dormant  in  the  protoplasm 
of  the  cells — energies  whose  multiplicity  the  investigations  of  our  own  times 
arc  constantly  impressing  upon  us. 

The  amount  of  decomposition  which  takes  place  in  the  cell  is  decided  alone 
by  the  energy  requirement  of  the  entire  organism,  so  that  the  total  consump- 
tion of  the  body  is  made  up  of  the  metabolism  of  all  the  cells.  These  cells. 
however,  show  a  wonderful  adjustment  to  the  requirement-  of  the  organism, 
not  only  quantitatively  but,  on  account  of  their  specific  properties,  qualita- 
tively as  well. 

It  is  not  the  oxygen  that  by  its  affinity  to  the  individual  constituents  of  the 
body  dominate-  the  chemical  processes  thai  occur  there.  If  oxygen  ruled,  the 
readily  oxidizable  substances,  such  as  uric  acid,  could  not  be  so  uniformly 
present  in  unaltered  form  in  the  excretions,  while  substances  which  are  ,,w\y 
oxidized  with  difficulty,  such  as  the  fats,  are  completely  burned.  It  is  the 
specific  force  contained  in  the  protoplasm  of  the  cells  which  causes  the  meta- 
bolic processes  in  the  animal  economy. 

Among  these  processes  the  -putting  up  of  complex  chemical  bodies  into 
simpler  bodies,  while  oxygen  is  at  the  same  time  taken  up.  plays  an  important 
role.  But  besides  mere  splitting  up,  and  splitting  up  with  absorption  of  water 
(hydrolytic  dissociation),  other  processes  of  reduction  and  synthesis  are 
largely  active,  and  occasionally  all  are  combined  in  a  -ingle  cell. 

Bence,  as  Rubner  maintained,  life  cannot  be  described  under  the  ereneral 
idea  oi  a  process  of  combustion  ;  we  must  rather  Bay  that  while  life  exists  there 
i-  constantly  an  employment  of  energy  and  a  transference  of  the  same  into 
other  forms  |  activity  and  heat). 

Physiologic  and  pathologic  chemistry  will  aid  us  still  further  in  analyzing 
the  chemical  changes  which  occur  during  the  processes  of  metabolism.  The 
'•volution  of  the  individual  protein  -iih-taiice-  contained  in  the  cell,  and  the 
disclosure  of  their  composition  by  the  production  of  split-products,  constitute 
the  one  method  which  ha-  keen  followed  with  success  in  solving  the  problems 
I"1'-"  involved.  Bui  the  protoplasm  of  the  living  cell  and  the  proteid  which 
we  have  produced  from  it  by  the  aid  of  our  chemical  method,  are  quite  differ- 
eiit  things.  So  also  the  products  of  decomposition  which  arise  in  the  destruc- 
tion of  the  cell  protoplasm  in  the  body  are  quite  differenl  from  those  which 
we  make  by  splitting  up  albuminous  Bubstance  in  a  test  tube.  In  the  one  case 
•  lead  albumin,  in  the  other  living  albumin  is  decomposed,  and  as  we  appre- 
ciate this  -rcat  difference  we  seem  to  drifl  yel  further  from  the  solution  of  the 

i Hofmeister,  "Chemie  der  lebenden  Zelle,"   Vortrag,  L901. 


4  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

problem  of  life.  Yet  even  here  the  ingenuity  of  our  scientists  has  found  a  way 
to  probe  more  deeply  into  the  cause  of  things,  and,  though  still  in  the  first 
stages,  the  most  recent  investigations  upon  organs  kept  alive  outside  the  body 
(saturated  with  blood,  autolysis)  have  been  followed  by  important  results 
which  permit  us  to  expect  more  surprising  conclusions  in  the  future. 

On  the  other  hand,  it  must  be  emphasized  that  although  our  knowledge 
of  the  chemical  processes  of  metabolism  is  still  comparatively  primitive,  the 
laws  of  metabolism  have  been  decidedly  advanced  by  a  more  physical  consid- 
eration of  the  processes.  The  dynamic  conception  of  the  transition  of  food 
products,  thought  out  by  Eubner,  furnished  a  basis  for  labors  in  the  clinical 
pathology  of  metabolism  upon  which  a  superstructure  might  be  raised  with 
ease  and  certainty,  and  upon  this  the  imposing  structure  of  modern  laws  of 
metabolism  in  the  diseased  body  was  soon  erected. 

If  we  take  this  as  our  actual  theme,  we  note  that  in  the  clinical  study  of 
metabolism  in  the  last  few  decades  quantitative  investigations  take  precedence. 

The  history  of  this  begins  with  the  publication  of  E.  Bischoff's  book, 
"Urea  as  the  Measure  of  Metabolism"  (1853).  The  method  of  estimating 
the  amount  of  urea  by  titration,  first  employed  by  J.  v.  Liebig,  enabled  Bischoff 
and  Voit  to  undertake  numerous  investigations  by  which  they  determined  the 
laws  of  nutrition  in  the  Carnivora.1 

Chossat  had  previously,  by  careful  experiments  with  starving  pigeons, 
demonstrated  the  daily  loss  of  weight  and  the  amount  of  the  excretions;  and 
Bidder  and  Schmidt  in  their  book,  "  The  Digestive  Fluids  and  Metabolism" 
(1852),  described  minutely  the  valuable  results  of  their  investigations  regard- 
ing the  metabolism  of  Carnivora  (cat)  under  the  most  varied  conditions  of 
nutrition.  They  were  the  first  to  relate  in  detail,  after  an  investigation  in 
which  all  requirements  were  fulfilled,  how  to  find  in  the  urine  and  the  feces 
the  nitrogen  ingested  in  food  in  the  form  of  meat,  and  upon  this  they  founded 
the  law  of  nitrogen  equilibrium. 

With  the  aid  of  the  elementary  analysis  of  urine  and  feces,  and  the  care- 
ful estimation  of  the  factors  of  respiratory  metabolism  which  were  made  pos- 
sible by  the  help  of  v.  Pettenkofer,  the  study  of  the  quantitative  analysis  of 
metabolism  in  Voit's  physiologic  laboratory  in  Munich  soon  attained  great 
technical  exactness.  With  this  came  the  facilities  for  studying  the  alterations 
of  decomposition  under  most  varying  circumstances,  and  particularly  with 
food  of  different  nature  and  quantity,  and  thus  it  became  possible  to  deter- 
mine the  laws  of  the  total  animal  economy. 

CONSUMPTION   OF   FOOD   IN  THE   HEALTHY 

A.     THE  LAWS  OF  NUTRITION 

The  estimation  of  the  amount  of  food  required  by  the  healthy  human  organ- 
ism to  maintain  its  equilibrium  has  been  the  subject  of  many  experiments  by 
Voit  and  his  pupils. 

i  Bischoff  u.  Voit,  "  Die  Gesetze  der  Ernährung  des  Fleischfressers,"   1880. 


COMSUMPTIOX  OF   FOOD  IN  THE  HEALTHY  5 

The  more  complete  the  technic,  and  the  more  ingenious  the  investi- 
gation, the  more  certainly  the  results  show  that  metabolism  is  determined 
by  the  activities  of  the  body  (heat  production  and  force).  Then  by  excluding 
all  external  factors  which  could  increase  metabolism,  it  is  shown  that  the 
"  resting-energy  "  *  of  metabolism  is  equivalent  in  its  potential  value  to  the 
amount  of  heat  produced.  This  has  unquestionably  been  proven  by  Kubner's 
calorimetric  investigations. 

In  rest,  the  dissipation  of  heat  is  the  only  avenue  for  loss  of  force.  Dis- 
sipation of  heat,  however,  is  a  function  of  the  surface  of  the  body.  If  it 
determines  the  ratio  of  metabolism  in  rest,  this  metabolism  must  in  turn  be 
dependent  upon  the  surface  of  the  body  (law  of  the  development  of  the  sur- 
face, Rubner). 

There  can  be  no  doubt  that  this  biologic  law  also  exists  in  pathology. 
Where  conspicuous  differences  in  the  amount  of  the  resting-energy  per  kilo- 
gram of  body-weight  exists,  an  attempt  should  be  made  to  explain  it  by  the 
variation  in  the  amount  of  surface  before  we  accept  the  view  that  a  special 
protoplasm,  characterized  by  a  more  active  or  sluggish  metabolism,  plays  a 
role  (in  nurslings,  in  obesity,  etc.). 

Table  I 

ENERGY  METABOLISM  PER  SQUARE  METER  OF  BODY  SURFACE' 


Atrophic  child  (cow's  milk). , 
Atrophic  child  (infant  milk), 

Breast-fed  child 

Normal  child  (cow's  milk). . 

Boy,  thin 

Boy,  fat , 

Man 

Man 

Man 

Man 

Man 


Weight  in 

kilograms. 

Calories  per 

twenty-four 

hours  in  one 

Bquare  meter. 

3 

1090 

8 

lose 

5 

1006 

8 

1143 

26 

1290 

41 

1278 

4!t3 

11801 

58 

1080* 

6?» 

1 1  >«;#;■» 

?13 

im;4 

978« 

The  metabolism  which  take  place  normally  in  the  body  of  a  mammal  when 
in  absolute  rest,  tor  the  purpose  of  maintaining  life,  is  always  the  same,  with- 
out regard  to  the  source  whence  it  obtains  the  organic  material  to  fulfil  its 
need — whether  from  albumin,  fat,  <>r  carbohydrates. 

For  the  maintenance  of  life  the  organic  food  products  compensate  accord- 
ing t<>  their  specific  energy  of  tension  (law  of  isodynamics) .  The  amount  of 
energy  which  the  individual   fond   products  contribute  to  the  processes  of 


1  German  :   Ruht  wt  rth. 

»  Rubner,  Beiträge  zur  "Ernährung  im  Knabenalter,"  Berlin,  1902,  j>.  62, 

>  Weight  with  clothing. 

*  Calculated  from  the  carbonic  acid  values. 


6  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

metabolism  that  arise  from  them,  and  by  their  combustion  in  metabolism 
becomes  living  force,  Rubner  has  calculated  at  4.1  calories  for  one  gram  of 
albumin,  9.3  calories  for  one  gram  of  fat,  4.1  calories  for  one  gram  of  carbo- 
hydrate. 

These  are  the  figures  which  are  utilized  as  standards  in  all  clinical  inves- 
tigations in  metabolism  (the  correspondence  of  the  value  for  albumin  and 
carbohydrate  is  quite  accidental). 

In  these  values  force  is  expressed  in  units  of  the  heat  which  is  generated  in 
the  organism  when  by  combustion  of  the  individual  food  products  their  end 
products  in  metabolism  are  produced.  The  loss  which  occurs  in  the  intestines 
by  insufficient  absorption  of  the  food  is  not  considered  here.  They  are,  there- 
fore, gross  values  (large  calories).  To  convert  them  into  pure  calories,  Rub- 
ner has  calculated  a  subtraction  of  8  per  cent,  from  the  average  heat  value  of 
the  feces  on  a  mixed  diet.  His  latest  investigations,  by  means  of  the  direct 
calorimetrv  in  man,  have  shown  that  the  calculation  obtained  from  chemical 
analysis  of  the  standard  figures  in  derived  heat  corresponds  almost  perfectly 
with  the  amount  of  heat  in  calories  taken  directly  from  the  calorimeter.  The 
method  commonly  used  in  the  clinic  to  calculate  the  energy  transference  from 
the  calory  value  of  the  food  introduced  is  therefore  accurate,  if  no  severe 
disturbances  in  absorption  are  present. 

B.    THE  METHODS  FOR  ESTIMATING  THE  CALORY  REQUIREMENT 

OF   THE  BODY 

The  method  in  use  in  Voit's  laboratory  for  determining  the  degree  of 
metabolism  in  a  healthy  individual  under  various  conditions  of  nutrition  is 
by  the  comparison  of  intake  and  output  in  a  trial  period  of  twenty-four  hours. 
This  presupposes  that  the  body  within  this  time  rids  itself  of  the  total  end 
products  of  metabolism  that  have  arisen  from  the  decomposition  of  organic 
substances.  This  supposition  is  quite  correct  for  excretion  in  the  respired  air 
and  in  the  urine.  To  estimate  the  contents  of  the  feces  (the  discharges  usu- 
ally occurring  Later  here),  we  need  to  mark  in  some  way  the  beginning  of  the 
experimental  period.  This  is  usually  accomplished  without  difficulty  and 
with  sufficient  exactness  by  the  administration  of  from  10  to  15  grams  of 
powdered  charcoal  or  0.3  gram  of  carmin  at  the  beginning  and  at  the  end  of 
the  metabolism  investigation.  This  method  in  its  high  technical  completion 
was  the  sine  qua  non  for  the  quantitative  investigation  of  metabolism  at  the 
bedside. 

An  accurate  estimate  of  the  food  ingested  during  the  period  of  trial  and 
of  the  carrier.  0f  energy  contained  in  it  (albumin,  fat  and  carbohydrates)  is 
necessary.  The  excretions,  i.e..  the  urine,  the  feces  and  the  expired  air,  are 
measured  with  exactness,  and  analyzed  as  to  the  amount  of  nitrogen  and  car- 
bonic acid  which  fchey  contain.  From  a  comparison  of  ingesta  and  excreta 
the  balance  is  obtained. 

1  shall  quote  an  example  of  one  of  Voit's  experiments:  A  workman  weigh- 
ing v.). ~>  kilograms  look  in  the  form  of  meat,  e^,  albumin,  milk,  bread,  lard, 
butter,  flour  and  sugar, a  total  of  137  grams  of  albumin,  117  grams  of  fat,  and 


CONSUMPTION   OF   FOOD  IN  THE  HEALTHY  7 

352  grams  of  carbohydrate,  containing  19.5  grams  of  X  and  315.5  grams 
of  C,  besides  2,016  grams  of  water.     He  excreted  in  complete  rest: 

In  the  urine 17.4  grams  N.,  12.7  grams  C,       1,279  grams  water. 

In  the  feces 2.1       "      N.,  14.5      "      C,  83      "       water. 

In  the  respiration 24*.6      "      C,  828      "      water. 

Total 19.5      "      N.,        275.8      "      C,       2,190      "      water. 

The  body  was,  therefore,  in  N-equilibrium ;  excreted  171  grams  of  water 
and  retained  39.8  grams  of  carbon,  which  corresponds  to  a  deposition  of  52 
grams  of  fat. 

This  method  gives  us  knowledge  of  the  body-albumin  during  the  investiga- 
tion. This  is  estimated  by  means  of  the  nitrogen  balance,  a  method  which, 
since  that  time,  has  come  into  general  use. 

One  hundred  grams  of  albumin  contain  16  grams  of  X.  If  the  entire 
amount  of  X  due  to  the  decomposition  of  albumin  during  the  trial  period 
were  excreted  in  the  urine,  the  X  figure  of  the  urine  need  only  be  multiplied 
by  6.25  to  determine  the  amount  of  albumin  metabolism.  The  other  X  losses 
of  the  body  arc  slight.  A  small  portion  appears  in  the  feces  as  a  residue  of 
the  intestinal  secretions  and  this  is  sufficiently  large  to  be  calculated  in  each 
investigation.  The  other  N  losses  of  the  body  (loss  of  hair,  scales  of  the 
epidermis  and  sweat)  are  so  insignificant  that  they  may  be  ignored  in  a  trial 
period  lasting  twenty-four  hours. 

Nitrogen  equilibrium  is  then  shown  when  the  food-X  =  urinary- X  -f- 
fecal-X. 

Yoit's  quantitative  met  bod  of  estimating  metabolism  also  permits  us  to 
recognize  from  the  carbon  balance  whether  the  body's  need  of  X-five  sub- 
stance has  been  fulfilled  by  the  food  given  during  the  trial  period  or  not. 
The  organism  has  its  very  definite  calory  requirement.  With  an  insufficient 
administration  of  nourishment,  the  body  takes  a  supply  of  energy  from  its 
own  material  component  parts.  When,  in  a  body  previously  in  equilibrium, 
carbon  is  retained  or  more  excreted  than  is  ingested,  a  corresponding  accumu- 
lation or  loss  of  fat  is  indicated.  In  the  form  of  carbohydrates  (glycogen)  the 
body  does  not  accumulate  any  great  supply  of  energy. 

In  the  quantitative  estimation  of  metabolism  in  the  clinic  it  has  been 
necessary  as  a  rule  to  proceed  without  determining  the  carbon  balance.  This 
requir«     the  estimation  of  the  total  ('<).  excretion  in  the  respired  air.  which 

can  oni\    he  accomplished   by   mean-  of  a  large  respiratory  apparatus  BUch   as 

that  of  Pettenkofer.  Such  an  apparatus  i-  expensive  and  very  difficult  to 
adjust.  As  many  hour-  are  required  to  make  the  experiment,  it  is  incon- 
venient to  employ  this  apparatus  at  the  bedside. 

To  compensate  for  this,  the  condition  of  the  body-weight  has  been  em- 
ployed as  a  control  to  determine  whether,  besides  the  proteid  requirement,  a 
sufficient  energy  supply  for  the  needs  of  the  organism  i-  present  in  the  food. 
If  there  is  little  variation   in  the  material   constituents  of  the  body   (albumin, 

fat  and  water),  this  i<  permissible,  especially  if  the  experimental  period  u 
not  too  brief.  [nstead  of  trial-  of  twenty-four  hours,  therefore,  trial  periods 
of  three  to  four  days  are  usual  in  metabol ism  analyses  of  this  type. 


8  ANALYSIS  OF   DISTURBANCES  OF  METABOLISM 

If  the  test  is  made  for  still  longer  periods,  the  weight  of  the  body  alone, 
with  minute  estimation  of  the  energy  value  of  the  food,  may  enable  us  to 
recognize  the  calory  requirement. 

Forster  demonstrated  in  persons  living  under  ordinary  conditions  the 
food  values  just  sufficient  to  maintain  weight  and  to  enable  them  to  follow 
their  usual  occupations.  In  numerous  investigations  with  larger  groups  of 
men  (in  barracks,  in  prisons  and  in  almshouses)  by  an  analysis  of  the  food 
ingested,  valuable  standards  have  been  established  for  the  amount  of  food 
required' by  healthy  persons.  If  the  individual  continues  as  vigorous  as  usual 
and  bis  body-weight  remains  unchanged  while  on  a  prescribed  diet,  the  con- 
tusion is  justifiable  that  the  amount  of  energy  contained  in  the  allotment 
of  food  is  sufficient  for  the  requirements  of  the  body. 

As  the  metabolism  of  the  body  depends  upon  the  needs  of  all  the  cells  in 
the  body,  and  represents  essentially  a  process  of  combustion,  it  is  obvious 
thai  the  intake  of  oxygen  should  also  be  considered  in  estimating  metabolism 
in  the  body.  But  the  estimation  of  oxygen  consumption  is  not  an  accurate 
measure  of  the  total  metabolism,  because  the  same  amount  of  oxygen,  accord- 
ins;  to  whether  it  is  utilized  for  the  oxidation  of  albumin,  fat  or  carbohy- 
drates, corresponds  to  different  quantities  of  heat;  also  because  one  gram  of 
expired  carbonic  acid,  according  as  it  has  been  formed  by  combustion  of  one 
or  another  food  stuff,  corresponds  to  very  different  degrees  of  heat. 

Therefore,  only  when  the  nature  of  the  food-materials  decomposed  in 
the  body  remains  the  same  are  consumption  of  oxygen  and  excretion  of  car- 
bonic acid  a  measure  for  changes  in  the  entire  consumption  of  products. 

By  means  of  the  large  respiratory  apparatus  of  Hoppe-Seyler-Tigerstedt, 
the  direct  estimation  of  all  the  factors  of  the  respiratory  metabolism  of  gases 
is  possible.  The  apparatus  is  difficult  to  manage,  however,  and  the  necessarily 
long  stay  in  the  chamber  of  the  person  experimented  upon  makes  its  use 
inconvenient;  therefore,  in  the  sick  but  few  observations  have  been  made 
on  this  plan. 

It  is  much  easier  to  estimate  the  absorption  of  oxygen  and  the  production 
of  carbonic  acid  with  the  apparatus  of  Zuntz  and  Geppert.  In  brief  experi- 
ments, trials  are  usually  made  by  means  of  a  mouth-piece  for  only  five  to  ten 
minutes,  at  most  for  one  hour;  the  02  and  C02  in  the  expired  and  inspired 
nir  and  the  amount  of  02  intake  and  C02  excretion  per  minute  are  calculated 
from  this. 

To  calculate  the  total  02  consumption  for  an  entire  day  from  these  figures 
would  lead  to  error,  on  account  of  the  great  variation  in  the  respiratory 
interchange  of  gases  from  hour  to  hour. 

Their  reciprocal  relation,  however,  furnishes  the  respiratory  quotient, 
which  gives  valuable  information  regarding  the  nature  of  the  material  de- 
composed at  the  time.  It  approaches  the  value  of  1.0  in  carbohydrate  com- 
Kustion.  while  during  the  combustion  of  albumin  alone  it  amounts  to  0.73, 
and  in  combustion  of  Eat  to  0.7. 

bor  the  quantitative  estimation  of  the  interchanges,  the  enormous  amount 
of  material  gathered  by  Zuntz  and  his  pupils  in  numerous  healthy  and  sick 
persons  contributes  valuable  points.    In  absolute  rest  of  the  body,  and  in  the 


CONSUMPTION  OF   FOOD  IN  THE   HEALTHY  9 

intervals  of  intestinal  inactivity,  which  occur  from  six  to  eight  hours  after 
meals,  the  values  for  the  intake  of  ( ).,  and  the  excretion  of  C02  per  minute 
are  quite  constant  for  any  healthy  individual,  and  in  different  healthy  indi- 
viduals they  vary  only  within  certain  limits.  In  these  "fasting  values"  we 
have  standard-,  variation  from  which  in  one  or  the  other  direction  denotes 
pathologic  change. 

In  conclusion,  direct  calorimetry  must  be  considered  as  the  exact  method 
by  which  to  determine  the  entire  transference  of  energy  in  the  resting  body. 
This  coincides,  as  already  mentioned,  with  the  total  loss  of  heat,  the  coinci- 
dence of  which  with  the  heat-equivalent  of  the  food  stuffs  consumed  have 
been  determined  by  Iiuhner  in  animals  by  masterly  experiments.  In  man, 
and  especially  in  the  sick,  direct  calorimetric  estimations  to  determine  the 
quantity  of  the  total  metabolism  have  heen  carried  out  only  in  isolated  cases 
(see  below). 

C.  THE  ENERGY  REQUIREMENT  OF  THE  HEALTHY 

The  quantity  of  fond  required  by  a  workman  while  performing"  moderate" 
labor  Yoit  stated  to  be  118  grams  of  albumin,  50  grams  of  fat.  and  500  grams 
of  carbohydrates.  This  was  based  upon  many  experiences  taken  from  daily 
life,  and  corresponds  with  the  results  of  numerous  exact  analyses  of  metab- 
olism carrier!  out,  according  to  the  method  described  above,  in  Yoifs  labora- 
tory (comparison  of  the  intake  and  output).  For  a  long  time  Voit's  princi- 
ples existed  almosi  as  a  dogma.  Later  the  total  calory  value  to  which  this 
diet  corresponds  (3,055  calories),  as  well  as  the  Large  amount  of  albumin 
contained  in  it,  became  the  subject  of  lively  discussion,  in  which  the  clinical 
investigators  took  a  prominent  part. 

If  the  performance  of  muscular  work  increases  the  energy  requirement 
of  the  body  above  that  of  resi  (and.  in  fact,  it  multiplies  several  times  the 
heat  equivalent  to  the  work  clone),  the  calory  requirement  of  the  v"  workman  ** 
cannot  he  estimated  otherwise  than  by  considering  the  amount  of  work  to 
he  performed.  The  rich  statistical  material  which  i-  now  at  hand  confirms 
the  requiremenl  of  Yoit  for  about  t3  calories  (which  is  the  amount  contained 
in  the  above  quantity  of  food  per  kilogram  of  body-weight)  for  persons  doing 
active  muscular  work. 

From  many  observations  Rubner  calculates  as  the  medium  amount  for 
a  twenty-four-houT  metabolism  in  the  healthy  adult,  of  average  body  size. 
and  weighing  1<»  kilograms : 

Pure  <  !alory  per 

calories.  kilogram. 

At  rest 2.:tici  =  82.9 

With  slight  muscular  work 2,446  =  84.9 

With  moderate  muscular  work 2.siiH  =  41.0 

With  exhausting  muscular  work -i.-W'i  =  18.0 

With  a  deduction  of  s  per  cent,  from  the  3,055  large  calories  which  are 
contained  in  Voit'a  amount  of  food,  this  corresponds  exactly  with  Rubner'e 
calculations. 


10  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

With  more  justice,  Voit's  requirement  of  118  grams  of  albumin  has  been 
the  subject  of  dispute.  In  the  discussion  regarding  this  amount  there  has 
been  much  difference  of  opinion.  In  their  conception  of  the  main  point  in 
dispute,  the  views  of  different  authors  were  diametrically  opposed;  and  the 
conflicting  opinions  which  arose  in  consequence  of  this  have  kept  the  discus- 
sion alive  to  the  present  time. 

In  the  food  of  man,  which  consists  of  albumin,  fat  and  carbohydrates, 
the  albumin  bodies  grouped  in  contrast  to  N-free  substances  are  especially 
important.  While  the  latter  may  be  compensated  for  to  a  great  extent  by 
each  other  and  also  by  albumin,  according  to  the  measure  of  their  energy 
value,  a  certain  quantity. of  albumin  in  the  daily  food  is  irreplaceable  and 
indispensable  if  the  proteids  of  the  body  are  to  be  maintained  intact. 

To  determine  this  indispensable  amount  of  albumin,  the  minimum  which 
the  body  requires  to  maintain  the  living  substance  in  a  functioning  condition 
has  been  the  subject  of  much  discussion. 

For  a  time  it  was  believed  (Bidder  and  Schmidt)  that  this  albumin  mini- 
mum corresponded  with  the  albumin-metabolism  of  persons  kept  in  a  state 
of  starvation,  i.  e.,  that  the  nitrogen  excretion  in  starvation  furnishes  a  stand- 
ard for  the  nitrogenous  metabolism  necessary  to  maintain  life,  that  is,  the 
actual  albumin  requirement  of  the  body.  All  the  albumin  absorbed  from  the 
intestine  in  excess  of  this  was  to  be  considered  "  luxury,"  and  was  supposed, 
like  the  N-free  substances,  to  undergo  prompt  combustion  in  the  blood  without 
becoming  organized  at  all. 

Among  clinicians,  no  less  a  one  than  Frerichs  upheld  this  theory  of  "lux- 
ury combustion/'  propounded  by  C.  G-.  Lehmann. 

Ynit  opposed  the  "  luxury  "  theory.  In  his  "  Handbook  of  the  Physiology 
of  Total  Metabolism  "  (page  269)  he  devotes  a  special  chapter  to  contradicting 
this,  and  furnishes  convincing  proofs. 

According  to  experiments  made  in  the  dog,  which  of  course  are  to  be  inter- 
preted somewhat  differently  from  human  experiments  and  which  in  their 
general  application  to  man  have  been  attacked  by  some  investigators,  the 
smallest  quantity  of  albumin  which  will  maintain  the  nitrogenous  equilibrium 
of  the  body  (on  a  mixed  diet  with  X-free  food  substances)  is  usually  2^  to  3 
times  larger  than  the  nitrogenous  metabolism  in  starvation.  In  their  com- 
prehensive experiments  E.  Voit  and  Korkunoff1  still  found  the  minimum 
albumin-requirement  to  be  111  per  cent,  greater  than  the  nitrogenous  metab- 
olism in  starvation  (and  even  with  very  large  amounts  of  starch  in  the  food). 

It  may  therefore  be  considered  as  proved  that  if  we  give  a  dog  only  the 
amount  of  proteid  which  is  decomposed  in  a  state  of  starvation,  this  amount 
is  llMt  Bufficienl  to  maintain  the  nitrogenous  equilibrium  of  the  body. 

In  man  the  same  appears  to  be  true.  With  sufficient  food,  the  excretion  of 
urea  is  increased  decidedly  above  the  starvation  figures.  From  this  experi- 
ence, and  upon  the  basis  of  investigations  on  the  nutrition  of  a  large  number 
of  workmen.   Voil  computed  as  a  standard  for  any  sufficient  diet  the  above- 


i  /•;.   I  oil  .-in,]  Korkunoff,  "  Die  geringste  zur  Erhaltung  des  Stickstoffgleichgewichtes 
nöthige  Menge  von  Eiweiss."    Zeitschr.  f.  Biol.,  xxxii,  p.  58. 


CONSUMPTION   OF  FOOD  IN  THE   HEALTHY  11 

mentioned  high  requirement  (hygienic  albumin  minimum  in  contrast  to  the 
ph  ys iolog ic  albumin  minimum ) . 

It  appears,  however,  that  proteid  metabolism  during  starvation,  even  in 
the  same  individual,  has  no  constant  height,  at  least  not  during  the  first  days 
of  fasting.  Here  it  apparently  depends  upon  the  composition  of  the  food 
which  has  preceded  the  experiment  and  on  the  food  products  retained  in  the 
body.  It  is  high  if,  in  the  days  preceding  the  fast,  a  large  amount  of 
albumin  has  been  ingested,  and  decidedly  smaller  if  for  a  long  time  prior  to 
the  starvation  period  the  ingestion  of  albumin  has  been  slight.  Only  after 
from  one  to  three  days  will  the  nitrogen  excretion  in  the  urine,  varying  in 
the  same  individual,  show  constant  figures.  This  constant  figure  apparently 
depends  on  the  com  position  of  the  body,  i.e..  its  albumin  and  fat  condition. 
From  this,  during  starvation,  it  must  make  up  its  losses. 

The  source  of  the  albumin  which  is  so  rapidly  decomposed  during  the  first 
days  of  starvation  is  not,  according  to  Vbit,  the  albumin  of  the  organs,  but 
the  much  more  easily  decomposed  and  soluble  albumin  of  the  fluids,  the  "  cir- 
culating "Ihn min."  This  quantity,  which  is  increased  by  a  diet  rich  in  albu- 
min, also  determines  the  proteid  metabolism  in  the  first  days  of  starvation. 

A  deficiency  of  albumin  in  the  food  diminishes  the  amount  of  "circulating 
albumin,"  and  as  this  is  dependent  upon  the  fixed  or  organic  albumin  it  indi- 
rectly works  mischief  upon  the  organs. 

A  superfluous  intake  of  albumin,  on  the  other  hand,  increases  the  amount 
of  the  readily  destroyed  circulating  albumin  in  the  fluids,  and  hence  propor- 
tional with  the  introduction  of  albumin  there  is  an  increased  albumin  decom- 
position which  is  dependent  upon  the  amount  of  circulating  albumin  and  the 
N-excretion  in  the  urine. 

The  amount  of  albumin  consumed  in  a  unit  of  time  in  the  animal  body  is 
dependent  to  an  astonishing  degree  upon  the  amount  of  the  albumin  ingested. 
The  capacity  of  the  normal  adult  organism  to  maintain  its  equilibrium  with 
any  amount  of  albumin — exceeding  the  minimum — is  hardly  limited  (in  30 
far  as  the  body's  capacity  to  take  up  albumin  permits  investigation).  If  the 
energy-requirement  of  the  organism  is  met  by  the  food,  the  proteid  of  food 
decomposes  completely  and  with  extraordinary  rapidity.  Scarcely  absorbed  in 
the  fluids,  it  i-  Boon  destroyed,  and  in  the  briefesl  time  its  nitrogenous  cleav- 
age products  appear  in  the  urine  for  excretion  in  quantities  corresponding 
exactly  with  the  increased  albumin  intake.  This  fact  forms  one  of  the  most 
important  point-  in  Vbitfs  whole  theory  of  nutrition;  important  both  for 
pathology  and  for  physiology.  Eence  it  became  at  once  the  -pur  for  many 
clinical  investigations  in  metabolism. 

Many  endeavors  have  been  made  to  explain  these  facts.  They  contradict 
completely  the  otherwise  applicable  law  that  the  amount  of  decomposition  in 
the  animal  body  is  equivalent   to  its  requirement  of  energy.     For  Vbit   has 

shown  that  with  a  BUfficient  amount  of  food  any  additional  amount  of  albu- 
min, no  matter  how  large,  is  at  once  decomposed,  bo  that  metabolism  (trans- 
ference of  energy)  is  greatly  increased. 

The  changes  in  the  total  metabolism  by  variation  of  the  intake  other 
than  those  referred  to  above  are  slight.     The  introduction  of  amount-  of 


12  ANALYSIS  OF   DISTURBANCES  OF  METABOLISM 

food  whose  heat-equivalent  is  not  decidedly  above  the  interchange  of  forces 
in  the  starving  organism  does  not  increase  the  total  metabolism,  and  with  a 
diet  beyond  the  amount  required  by  the  needs  of  the  body  the  introduction 
of  extra  X-free  material  (fat  and  carbohydrates),  no  matter  how  great,  in- 
creases the  interchange  of  energy  only  to  a  certain  percentage  of  the  excess 
of  food. 

If  the  surplus  is  introduced  in  the  form  of  fat,  only  10.7  per  cent,  of  it 
undergoes  combustion;  therefore  almost  90  per  cent,  is  deposited  as  fat  in 
the  body.  If  superfluous  carbohydrates  are  introduced,  only  15.9  per  cent. 
goes  to  increase  the  total  metabolism;  84.1  per  cent,  is  accumulated  in  the 
body  and  is  utilized  for  fat  formation,  since  the  body's  capacity  to  increase 
its  carbohydrate  material  (glycogen  deposit)  is  a  limited  one.1 

Since  the  amount  of  metabolism  is  relatively  independent  of  variations  in 
the  ingestion  of  nourishment,  we  have  the  conditions  which  make  possible  a 
deposition  of  fat. 

With  an  abundant  introduction  of  albumin,  however,  proteid  decomposi- 
tion increases  in  exact  ratio  to  the  superfluous  amount  of  albumin  ingested. 
The  entire  superfluous  supply  is  taken  up  in  metabolism,  and  the  N-excretion 
in  the  urine  shows  a  height  corresponding  to  the  increased  administration. 

In  reality  it  is,  of  course,  only  the  N-containing  complex  in  albumin  which 
is  excreted,  and  these  products  of  excretion  are  at  once  thrown  off.  Of  the 
non-nitrogenous  components  which  remain  after  excretion,  as  well  as  also 
the  superfluous  fat  and  carbohydrates  introduced,  only  a  portion  is  subjected 
to  decomposition,  if  the  organism  does  not  require  them  to  meet  its  energy 
requirements,  while  a  considerable  remainder  ((39.1  per  cent.)  is  stored  up  in 
the  body  ( fat  formation  from  albumin).  Only  the  elimination  of  nitrogen  is 
complete. 

For  this  reason  albumin  occupies  an  exceptional  position  among  food  sub- 
stances ;  the  organism  requires  it  for  its  simple  material  maintenance.  It  is, 
therefore,  difficult  to  understand  why  the  organism  should  waste  so  much  of, 
and  so  soon  eliminate,  this  most  valuable  food  product. 

A  number  of  explanations  for  this  apparent  waste  have  been  offered.  It 
has  been  assumed  that  owing  to  the  circulation  of  albumin  products  in  the 
fluids  after  albumin  nutrition,  the  individual  food  stuffs  take  part  in  the 
total  metabolism.  On  the  other  hand,  a  special  chemical  affinity  of  the  cell 
substance  for  the  individual  food  products  has  been  assumed  owing  to  the 
fact  that  the  albumin  is  most  readily  absorbed,  less  speedily  the  carbohydrates, 
and  last  of  all  the  fats. 

Kühner-  has  lately  assumed  that  the  divisibility  of  the  individual  food 
stuff-  explains  the  different  share  taken  by  each  in  the  processes  of  metabo- 
lism.  These  differences  in  divisibility  have  not  been  sufficiently  considered 
until  now:  "A  measure  of  these  differences  is  the  size  of  the  molecules.  In 
the  case  of  fat  this  amounts  to  870,  in  grape  sugar,  to  only  180.     In  what 

•  Tlii-  increase  in  metabolism  by  introduction  of  food  was  formerly  explained  by  an 
increase  of  intestinal  activity.     Lately  the  correctness  of  this  view  has  been  doubted. 
2 Bubner,  "Handbuch  der  Ernährungstherapie,"  Bd.  i,  p.  78. 


CONSUMPTION*  OF  FOOD  IX  THE  HEALTHY  13 

form  the  albumin  products  circulate  is  not  known.  Nevertheless,  the  view 
that  albumin  and  allied  substances  arc  always  bodies  of  high  atomic  weight, 
has  suffered  a  setback.  The  albumoses  have  a  molecular  weight  of  from  1.200 
to  2,100;  the  peptones,  however,  of  only  about  200,  similar  to  that  of  sugar. 
In  a  molecule  of  fat  there  are  8,1  To  calorics,  in  a  molecule  of  grape  sugar 
only  674.  The  peptones  vary  very  slightly  from  the  latter  value.  The  vari- 
eties of  sugar  and  albumin,  therefore,  viewed  from  this  standpoint,  might 
predominate  in  decomposition  without  special  forces  coming  into  play.'" 

Gruber1  looks  upon  the  prompt  splitting  up  of  the  albumin  of  food  as  a 
very  necessary  process,  in  fad  as  an  arrangement  which  is  <piite  indispensable 
to  rid  the  organism  as  soon  as  possible  of  the  great  bulk  of  soluble  albumin 
bodies  which  are  unnecessary  for  its  normal  condition  and  which  cannot  be 
utilized.  A  further  increase  in  the  si/«'  of  the  organs  in  the  adult  animal  is 
possible  only  to  a  slight  degree  after  the  body  has  reached  the  limit  of  growth 
fixed  by  its  hereditary  germinal  predisposition  (increase  of  the  size  of  muscles 
as  the  result  of  body  exercise).  To  replace  the  amount  of  organic  albumin 
daily  destroyed  a  small  portion  of  the  food  proteid  is  sufficient.  As  the  accu- 
mulation of  the  balance  in  the  body  would  alter  the  function  of  the  organs, 
its  immediate  decomposition  is  absolutely  necessary  in  order  to  keep  the  com- 
position and  concentration  of  the  body  fluids  unchanged  in  spite  of  any  varia- 
tion in  the  composition  of  the  food. 

The  prompt  splitting  up  of  the  food  albumin  is  believed  by  Gruber  to  be 
the  effect  of  the  action  of  enzymes  with  which  tin1  cells  of  the  adult  healthy 
organism  are  richly  supplied.  This  view  has  much  to  commend  it.  We  can 
thus  readily  explain  the  enormous  albumin  accumulation  which  occurs  in 
convalescence  from  severe  diseases,  after  prolonged  starvation,  etc..  and  is 
almosl  independent  of  the  administration  of  albumin.  The  absence  of  the 
albumin-splitting  enzyme  in  body  cells  that  have  been  damaged  in  their 
proteid  constituent-  by  disease  explains  the  absence  of  that  rapid  splitting  and 
excretion  of  proteids  which  occurs  in  health. 

D.     THE   ALBUMIN   MINIMUM 

We  have  seen  that  Voit's  requirement  of  lis  grams  of  albumin  in  the 
daily  food  of  an  adult   performing  moderate  labor  is  a  practical  proposition 

for  rational  nutrition,  and  doe-  not  represent  the  physiologic  albumin  mini- 
mum which  the  mature  body  absolutely  requires  to  supply  it-  functioning 
organs,  [ncorrectly  viewed,  this  stimulated  a  great  number  of  researches  in 
which  the  starting  point  «ras  the  question  (although  it  can  have  only  the- 
oretic interest),  How  far  may  the  albumin  metabolism  he  decreased  without 
the  body  suffering  in  any  of  it-  albumin  constituents?  Ami  yet  every  new 
investigator  in  the  solution  of  this  question  attempts  to  establish  a  standard 
and  to  proclaim  a  still  lower  value  a-  the  "albumin  minimum.'*  That  man 
may  exist  with  -mailer  quantities  of  albumin,  and  he  capable  of  work,  Voit 
himself  readily  determined  in  the  analysis  of  metabolism  in  a  vegetarian  who 

i Gruber,  "Einige  Bemerkungen  /.um  Biweissstoffwechsel."  Zeitschr.  f.  />'/"/..  \lü. 
p.  407. 


14 


ANALYSIS   OF  DISTURBANCES  OF  METABOLISM 


weighed  57  kilograms.  Choosing  his  diet  freely  this  person  consumed,  year 
in,  year  out,  only  54.2  grams  of  albumin  (with  32.4  grams  of  pure  albumin), 
22  grams  of  fat  and  557  grams  of  carbohydrates,  and  maintained  the  same 
body-weight. 

The  investigations  in  metabolism  of  Hirschfeld,  Klemperer,  Peschel, 
Kumagawa,  Breisacher,  and  lately  also  of  Siven  and  Albu,  give  even  smaller 
values  as  the  albumin  minimum.  The  following  table  is  a  comparative  com- 
pilation of  the  food  values  with  which  individual  persons  experimented  upon 
were  able  to  maintain  their  N-equilibrium. 

Table  II 


Hirschfeld.. . 

Klemperer  I. 
Klemperer  II 

Peschel 

Kumagawa  . 

Voit... 

Breisacher  . . 

Siven 

Albu 


Body 
weight. 


73.0 
63.0 
65.0 
79.5 
48.0 
57.0 
57.0 
58.9 
37.5 


Albumin. 


35.4 
25.1 
26.6 
34.2 
37.8 
32.4 
51.4 
28.3 
43.13 


Albumin 
per  kgm. 


0.485 

0.400 

0.41 

0.43 

0.788 

0.570 

0.900 

0.48 

0.90 


Large  calories 
per  kgm. 


47.4 
80.0 
77.2 
47.1 
51.6 
47.5 
50.3 
41.4 
37.32 


Duration 
of  trial. 


8  days 


Usual  diet 

30  days 

1  day 

5  days 


The  albumin  interchange  in  the  professional  fasters,  Cetti  and  Breithaupt 

(calculated  from  the  N-figures  of  the  urine  by  multiplying  by  6.25),  gave 
on  the  other  hand : x 


Cetti. 

Breithaupt. 

First  day 
Second 

of  starvation 

95.3  grams  albumin 

79.3  " 
82.7      " 
78.1       " 

67.4  " 
63.6      " 

68.6  " 

56.1  " 

68.2  " 

59.7  " 

63.1  grams 
62.5       " 
83.7      " 
80.5      " 
68.9      " 

62.2  " 

albumin 

Third 

» 

« 

Fourth    ' 

n 

si 

Fifth 

a 

a 

Sixth- 

(( 

a 

Seventh  ' 

« 

Eighth     ' 
Ninth 

a 

u 

Tenth      ' 

i            l( 

Therefore,  it  is  evident  from  the  table  that  with  a  sufficient  calory  admin- 
istration  in  fond  products  free  of  nitrogen  the  albumin  requirement  may  fall 
far  below  lis  grams,  and  even  below  the  metabolism  under  complete  with- 
drawal of  food. 

Theoretically  this  fact,  determined  by  such  numerous,  painstaking  inves- 
tigations, is  of  the  greatest  scientific  interest.  But  caution  has  been  quite 
properly  enjoined  upon  us  not  to  draw  far-reaching  conclusions  from  such 


i  "  Untersuchungen   an   zwei   hungernden  Menschen." 
Suppl.-Heft,  pp.  21  u.  68. 


Yirchoio's   Arch.,   vol.   cxxxi, 


CONSUMPTION  OF   FOOD  IN  THE  HEALTHY  15 

brief  investigations  of  the  practical  laws  of  nutrition.  We  need  not,  with 
Pflüger,  assign  to  albumin  a  pre-eminent  importance  "  as  the  only  and  imme- 
diate source  of  muscular  power,"  but,  for  the  permanent  nutrition  of  the 
healthy  and  the  sick,  we  must  still  insist  upon  greater  amounts  of  albumin 
than  proved  sufficient  to  maintain  the  albumin  condition  of  the  body  in  the 
experiments  above  cited. 

In  fact  it  is  hardly  possible  to  transfer  the  conditions  of  an  experiment 
to  practice,  and  to  find  a  diet  that  will  give  a  sufficient  degree  of  energy  to 
the  body,  that  will  agree,  that  will  continuously  be  palatable  and  can  be 
digested,  yet  will  contain  such  slight  amounts  of  albumin  as  were,  for  exam- 
ple, present  in  the  experiments  of  Siven. 

This,  however,  may  be  seen  from  all  of  the  previously  mentioned  experi- 
ments— that  the  X-e<|uilibrium  can  only  be  maintained  on  such  a  low  proteid 
diet  when  we  have  a  sufficient  calory  supply.  In  most  experiments  the  calory 
value  of  the  food  reaches  the  amount  which  Voit  requires  for  the  "  medium 
worker'*  (with  nine  to  ten  hours'  daily  labor),  although  the  persons  experi- 
mented upon  did  not  perform  very  laborious  work;  in  a  few  experiments 
it  decidedly  exceeds  this  amount, 

Therefore,  only  with  a  superfluous  calory  administration  can  the  albumin 
metabolism  be  diminished  to  such  slight  values. 

The  calory  carriers,  carbohydrates  and  fat.  are  therefore  albumin  sums. 
and  for  practical  nutrition  this  is  perhaps  the  most  important  conclusion  of 
these  investigations  regarding  the  albumin  minimum. 

E.     THE   REQUIREMENTS   FOR   ALBUMIN   DEPOSITION 

According  to  A'oit's  law.  the  addition  of  albumin  to  a  did  already  suffi- 
cient increases  albumin  metabolism  to  such  an  extent  tbat  after  a  l'>'\v  .lavs 
N-equilibrium  is  again  reached,  vet  no  decided  accumulation  of  albumin 
occurs.  Bui  we  should  note  here  in  the  increase  of  the  energy  value  of  the 
food  by  the  addition  of  fats  and  carbohydrates  a  process  to  diminish  albumin 
metabolism,  so  that  when  albumin  administration  remains  the  same,  albumin 
deposition  musl  be  ihr  consequence.  This  gives  as  reason  to  hope  to  inert 
the  body  albumin  by  forced  feeding. 

I  nloriunatelv  the  energy  supply  contained  in  the  superfluous  food  which 
w  utilized  in  albumin  deposition  is  not  very  great,  a-  is  shown  by  Voifs 
investigations  in  the  dog.  With  the  addition  of  carbohydrates  upon  an  aver- 
:l--"  91-5  per  cent.,  and  with  the  addition  of  fats  upon  an  average  !»:>  per 
oent.  of  tl„.  superfluous  potential  energy  accumulates  in  the  form  of  fat.  and 
onlv  8-5  ''"'  '»  fad  only  :»  per  cent.)  in  the  tun,,  0f  albumin.  In  man 
according  to  the  investigations  of  v.  Noorden,1  at  most  10  per  cent,  of  the 
superfluous  energy  supply  is  utilized  to  store  up  albumin  in  the  body. 

The  experiment.  0f    KjUg J    upon    himself,    under    v.    Noorden'8   direction. 

i  r.   Voorden,  "Verhandlung,  der  physiol.  Qeselschaft,"  im  Arch.  f.    Inai    u    PhuH- 
obuju-,  1893. 

-  Krug,  "  Ueber  Fleischmad  beim  Menschen."    \.  \ den'a  Beiträge  /.  -  Lehn  vom 

Stoffwechsel,"  licit  2. 


16  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

have  shown,  however,  that  a  slight  accumulation  of  albumin  day  by  day  can 
be  attained  by  giving  a  food  of  high  calory  value  for  a  long  time.  With  food 
which  differed  from  that  of  the  prior  period  (when  he  was  in  N-equilibrium) 
by  an  increase  of  1,710  calories,  albumin  remaining  the  same,  Krug  retained 
decided  X-amounts  (a  total  of  about  50  grams  in  fifteen  days)  and,  what  is 
remarkable,  the  gain  during  the  last  of  the  fifteen  days  of  forced  feeding 
equalled  that  of  the  first  days. 

Lüthje  1  has  lately  obtained  still  larger  ^-retention  in  his  forced  feeding 
experiments  in  which  he  increased  the  total  energy  administration  of  the 
food,  like  Krug,  and  also  raised  the  quantity  of  albumin  decidedly  above  the 
requirement  (albumin  administration  up  to  380  grams  with  6,035  calories). 
The  total  retention  in  twenty-six  days  amounted  to  149.61  grams  of  N. 

This  decided  N-retention  within  a  short  time,  even  more  than  the  small 
values  formerly  obtained,  raised  doubts  as  to  whether  the  N  retained  in  the 
body  actually  indicated  a  gain  in  "  flesh." 

Voit  has  never  regarded  the  N-retention  obtained  by  forced  feeding  as  an 
increase  of  "organic  albumin";  he  held  the  view  that  the  albumin  saved 
under  the  influence  of  nutrition  remained  in  the  circulation  until  it  was 
changed  into  organic  albumin  by  the  slow  production  of  new  tissue.  As, 
however,  under  the  influence  of  hypernutrition,  the  plasma  of  blood  and 
lymph  does  not,  so  far  as  we  know,  become  richer  in  albumin,  v.  Noorden 
proposed  the  hypothesis  that  the  albumin  which  is  saved,  and  not  yet  utilized 
for  the  structure  of  new  tissue,  is  retained  as  a  dead  mass  in  the  living  proto- 
plasm of  the  cells,  analogous  to  the  superfluous  glycogen  and  fat,  remaining 
there  as  "  reserve  albumin,"  though  with  decidedly  different  conditions  of  de- 
composition than  are  present  in  organic  albumin.  Correspondingly,  he 
draws  a  sharp  distinction  between  increase  of  "  reserve  albumin "  and  in- 
crease of  muscle  (by  which  he  understands  the  increase  of  living  cell  albumin). 
He  believes  the  latter  to  be  a  result  of  the  specific  growth  energy  of  the  cells, 
a  function  of  cellular  labor,  and  not  a  result  of  extra  nutrition  since,  as  we 
have  seen,  hypernutrition  increases  only  the  reserve  albumin. 

This  hypothesis  of  v.  Noorden's  is  not  in  agreement  with  Pflüger's  2  view 
regarding  the  meaning  of  the  reserved  and  deposited  albumin.  In  the  latter's 
numerous  publications  on  the  subject,  he  maintained  that  the  accumulated 
albumin  is  soon  deposited  as  cell  substance  in  the  body  of  the  animal,  and 
therefore  at  once  takes  a  prominent  part  in  the  total  metabolism.  Pflüger 
does  not  regard  it  as  a  dead  cell  inclusion,  but  as  a  "  working  mass,"  and  he 
also  thus  explains  the  increase  of  albumin  metabolism  which  occurs  after 
proteid  administration  as  an  increase  of  the  "  working  cell  substance,"  upon 
the  amount  of  which,  in  his  opinion,  the  total  metabolism  is  directly  de- 
pendent. 

i  Lüthje,  Beitrüge  zur  "  Kenntnis*  des  Eiweissstoffwechsels."  Zcitschr.  f.  klin. 
Med.,  xliv,  p.  21. 

-  I'ßiiger.  Arch.  f.  d.  ges.  Phys.,  Bd.  lii,  p.  1.  "  Ueber  einige  Gesetze  des  Eiweiss- 
stoffwechsels," Bd.  liv,  p.  333.  "  Ueber  den  Einfluss,  welchen  Menge  und  Art  der 
Nahrung  auf  die  Grösse  des  Stoffwechsels  und  der  Leistungsfähigkeit  ausüben." 
Pfläger'8  Arch.,  Bd.  lxxvii,  p.  425. 


CONSUMPTION   OF   FOOD  IN  THE  HEALTHY  17 

But  the  enormous  amount  of  X-retention  in  the  forced  feeding  investi- 
gations of  Lüthje  makes  us  hesitate  to  believe  that  the  total  amount  of 
nitrogen  retained  is  really  deposited  as  "albumin,"  especially  as  we  should  be 
forced  to  assume  at  the  same  time  that  the  reserved  albumin  is  deposited 
together  with  a  quantity  of  water,  such  as  corresponds  to  the  usual  relation 
between  albumin  and  water  in  the  cellular  elements  of  the  body  (one  gram 
of  N  =  6.25  grams,  albumin  =  29.4  grams  of  flesh). 

According  to  this  we  should  have  to  suppose  that  the  X-retention  of 
149.61  grams  X,  which  was  attained  by  Lüthje  within  Twenty-six  days,  corre- 
sponded to  an  albumin  deposition  of  935.06  grams  of  albumin,  or  a  flesh 
deposition  of  4,398.53  grams.  The  increase  in  the  body-weight  of  the  person 
experimented  on  amounted  to  6,070  grams  during  this  time.  If  we  estimate 
the  flesh  accumulation  from  the  X-reteiit  ion.  more  than  two-thirds  of  the 
increase  in  body-weight  (4,398  grams)  must  have  been  due  to  flesh  deposi- 
tion. The  considerable  calory  excess  contained  in  the  administration  of  food 
in  the  days  in  question  certainly  must  have  resulted  in  a  deposition  of  fat. 
The  amount  of  this  Lüthje  calculates  in  the  usual  manner;  from  the  total 
calory  excess  during  the  entire  period  (29.656  calories)  he  deducts  the  calory 
value  of  the  albumin  which  has  accumulated  (935.06  X  4.1),  i.e.,  in  round 
number  3,838  calories,  and  the  remainder,  amounting  to  25.818  calo- 
ries, is  ascribed  to  fat  accumulation.  Twenty-seven  hundred  and  seventy-six 
grams  of  fat  correspond  to  this  energy  value.  The  flesh  accumulation  of 
4,398  grams,  and  a  simultaneous  fat  deposition  of  2,776  grams  coincide 
very  imperfectly  with  an  increase  in  weight  of  only  6,070  grams.  This  may, 
however,  be  readily  explained  by  the  assumption  that  the  body  during  the 
masting  period  lost  a  weight  of  water,  corresponding  to  the  difference  (  1,104 
grams). 

In  the  feeding  experiments  of  Krug,  the  same  difference  was  noted. 
With  an  increase  in  weight  of  only  3,100  grams,  the  albumin  accumulation  of 
1,455  grams  calculated  from  the  retained  \.  and  the  fat  accumulation  from 
the  calory  excess  after  deducting  the  albumin  calory,  amounted  to  2,254 
grams.  Krug  assumed  without  more  ado  that  the  body  lost  609  grams  of 
water. 

This  assumption  is  certainly  justifiable,  and  a  decrease  in  water  during 
forced  feeding  appeal--  quite  plausible  if  we  remember  thai  each  increase  of 
the  albumin  metabolism  (for  example,  by  a  Large  albumin  meal)  is  soon  fol- 
lowed by  a  decided  excrel ion  of  water. 

In  1 1 iy  opinion  the  assumption  of  so  large  a  loss  of  water  is,  however,  unnec- 
essary. In  the  previously  mentioned  calculation-,  we  have  always  proceeded 
on  the  assumption  that  the  total  calory  excess  of  the  food  nol  used  to  -tore 
up  albumin  musl  be  utilized  in  fat  formation.  It  has.  however,  nol  I o  con- 
sidered thai  an  excess  of  food  also  invariably  increases  the  total  metabolism, 
and.  it  may  now  be  supposed,  increases  this  oul  of  proportion  to  the  intestinal 

labor.    A  true  luxury  consumption  of  non-nitrogenous  f I  substances  takes 

place.  Only  a  portion  of  the  superfluous  food  energy  is  utilized  in  accumu- 
lation; in  man  another  portion,  probably  showing  individual  variation,  under- 
goes combustion,  and  is  utilized  in  heat   production,  the  organism  replying 


18  ANALYSIS  OF   DISTURBANCES  OF  METABOLISM 

to  this  increase  by  an  increased  excretion  of  vapor.  In  the  investigations  in 
forced  feeding,  the  fat  accumulation,  which  can  only  he  controlled  by  an 
accurate  estimation  of  the  carbon  balance',  may  also  be  less  than  authors  have 
assumed,  judging  by  the  caloric  excess  in  the  food. 

In  such  a  profuse  N-retention,  the  supposition  that  the  accumulation  of 
nitrogen-containing  end  products  of  albumin  metabolism  may  play  a  role 
appears  to  be  quite  unwarranted  for  the  reason  that  there  are  no  sufficient 
proofs  that  N-containing  products  of  intermediary  albumin  metabolism  re- 
main as  such  in  large  quantities  in  the  body  of  the  healthy.  The  view  is 
much  more  likely  that  the  N  is  retained  as  albumin,  and  that  this  albumin 
(as  a  native  molecule,  however,  and  without  a  corresponding  participation  of 
water)  enters  the  cell.  As  evidence  of  this  Lüthje  points  to  the  observation 
that  in  certain  snails  albumin  is  found  included  in  the  cells  in  a  crystalline 
form. 

It  seems  to  me;  however,  that  there  is  one  phenomenon — which  appears,  so 
far  as  I  am  aware,  in  all  investigations  regarding  albumin  accumulation  if  the 
analyses  in  question  are  carried  out — and  which  goes  to  show  that  the  albu- 
min accumulated  in  the  protoplasm  of  the  cells  increases  and  rejuvenates  it 
while  assimilating  itself  with  the  general  cell  albumin.  I  refer  to  the  simul- 
taneous retention  of  phosphorus  when  N  is  retained,  and  its  increased  excre- 
tion (as  P205)  during  albumin  decrease.  This  is  shown  in  the  investigations 
of  Kayser,  and  of  Jacob  and  Bergell.  It  may  be  recognized  also  in  Luthje's 
metabolism  figures,  and  only  lately  Kaufmann  has  called  attention  to  the 
decided  phosphorus  retention  which  he  observed  during  albumin  accumulation 
in  feeding  with  egg  albumin.  The  fact  that  any  phosphorus  containing  albu- 
min body  especially  favors  albumin  accumulation  (as  was  shown  by  Kbhmann 
and  his  pupils,  and  also  by  Zuntz  and  Caspari)  favors  this  view. 

Quite  an  analogous  N-retention  (which  probably  no  one  will  doubt  means 
an  albumin  accumulation)  Eost *  has  observed  in  his  metabolism  control 
experiments  in  growing  animals. 

The  amounts  of  nitrogen  of  the  food  which  were  not  excreted  in  the  urine 
and  feces  of  three  young  dogs  were  decidedly  greater  than  could  be  accounted 
for  by  the  increase  of  body-weight,  if  the  N-accumulation  were  reckoned  in 
the  formation  of  muscle  albumin.  Therefore,  as  in  the  investigations  of 
Lüthje,  either  a  loss  of  water  occurred  or  the  retained  nitrogen  was  utilized 
to  build  up  a  cell  protoplasm  with  higher  nitrogen  contents  than  are  found  in 
muscular  substance. 

When  it  became  necessary,  in  forced  feeding  experiments  in  animals  with 
meat  free  of  fat,  to  promulgate  a  formula  for  the  N-accumulation  (Pfliiger, 
Cremer)  certain  difficulties  naturally  arose.  The  amount  of  carbon  retained 
in  the  organs  was  greater  in  comparison  with  the  nitrogen  than  would  corre- 
spond to  the  composition  of  albumin. 

If,  with  Pfliiger,  we  reject  the  possibility  of  a  fat  formation  from  albu- 
min, although  accepted  by  Voit's  adherents,  we  must  be  content  with  assum- 


i  Rost,  "  Zur  Kenntniss  des   Stoffwechsels  wachsender   Hunde."      Veröffentlichungen 
des  kaiserl.  Gesundheitsamtes,  Bd.  xviii,  p.  206. 


CONSUMPTION   OF  FOOD   IN   THE   HEALTHY  19 

ing  an  "  unknown  tissue-building  substance,"  and  refer  the  ^-retention  to  its 
accumulation. 

No  matter  in  what  form  the  nitrogen  accumulates  in  the  body  in  forced 
feeding,  all  authors  seem  to  be  unanimous  in  the  opinion  that  the  organism 
receives  a  valuable  addition. 

For  this  reason,  we  shall  enumerate  again  the  methods  which  lead  to  an 
increase  of  the  body  albumin. 

We  sec  NT-retention  without  any  increase  in  the  administration  of 
nitrogenous  food-  when  we  give  a  calory  exec--  of  tT-free  substances  (Krug). 
and  a  still  more  decided  ^-accumulation  when  the  food  contains  both  an 
excessive  calory  value  and  an  excess  of  albumin  (Lüthje). 

That  an  excess  of.  albumin  alone  in  an  adult  healthy  person  withoul  de- 
cided increase  of  the  albumin-saving  fats  and  carbohydrates  could  bring  about 
an  albumin  accumulation  (apart  from  the  slight  N"-retention  in  the  first 
days,  until  N-equilibrium  is  attained)  lias  been  looked  upon  as  impossible, 
according  to  Voit's  principle«.  Only  special  circumstances  (growth,  con- 
valescence, diminution  in  body  albumin  from  preceding  starvation)  would 
make  it  possible  permanently  to  accumulate  albumin  in  this  way. 

Bornstein,1  however,  Lately  showed  in  an  experiment  on  himself  thai  it 
is  possible  in  man  by  an  increased  administration  of  albumin  alone  to  produce  a 
limited  increase  of  the  albumin  content-  of  the  body.  By  adding  to  his  diet 
50  grams  of  nutrose  daily  he  accumulated  in  fourteen  days  Hi  grams  of 
N  =  100  gram-  of  albumin,  just  as.  in  Pfluger's  experiments  in  feeding  adult 
animal-  (dog  and  cat)  with  fat-free  meat,  a  decided  increase  in  weighi  was 
produced  by  Hob  deposition.  And  as  Pflüger  looks  upon  the  increase  of  the 
albumin  mas-  of  the  body  as  an  increase  of  power,  so  Bornstein  looks  upon 
the  ^-accumulation  as  a  sign  of  ;i  previously  sub-standard  value  of  his  mus- 
cular and  albumin  apparatus,  which  was  then  improved  by  a  deposition  of 
albumin. 

h  is  an  interesting  fact  that  stock  raisers2  to-day  also  believe  it  possible 
to  bring  about  a  production  of  flesh,  in  a  restricted  -en-.'  of  the  word  and 
under  certain  circumstances,  in  adult  animal-  to  a  more  decided  extent  than 
was  formerly  though!  possible.  They  regard  an  increased  accumulation  of 
albumin  in  the  body  of  the  adult  animal  a-  decidedly  improving  the  quality 
of  the  meat— an  improvemenl  which  doe-  not  depend  upon  an  increase  in 
muscle  bulk  or  new  formation  of  muscle  libers,  but  is  due  to  an  inen 
of  the  juice-  in  which  the  muscular  fibers  are  bathed. 

For  the  physician  these  view-  regarding  muscle  food  are  very  interesting, 
inasmuch  a-  n  i-  often  necessary  for  him  to  treal  persons  below  par  in  their 
muscular  activity.  In  cases  in  winch  a  further  accumulation  of  fat  i-  never 
desirable  (anemia,  neurasthenia,  etc.),  Bornstein's  advice  to  adopl  forced 
feeding  with  a  decided  addition  of  albumin  i-  certainly  worthy  of  considera- 


'  Bornstein,  "Ueber  «lie  Möglichkeil  der  Biweissmast."     Berliner  klin,  Wochenechr., 
1898,  vol.  i\.  p.  7:0. 

-  Hi  inn  in  rii  iiti«!  Pfeiffer,  Journal  f.  Landwirthschaft,  Bd.  wwiii. 


20  ANALYSIS  OF   DISTURBANCES  OF  METABOLISM 

tion.  It  increases  the  albumin  contents  of  the  body,  and  also  the  albumin 
decomposition.  We  know  that  a  man  called  on  to  perforin  work  beyond  the 
usual  amount  always  prefers  a  diet  rich  in  albumin  (the  average  albumin 
metabolism  in  athletes  is  about  200  grams  of  albumin)  1  and  this  coincides 
perfectly  with  the  views  of  Pflüger  that,  "increased  albumin  decomposition  is 
combined  with  that  increased  vitality  which  in  the  struggle  for  existence  gains 
the  victory."  2 

More  exact  and  recent  investigations  in  metabolism  show  that  the  general 
tendency  of  working  organs  to  attract  albumin  and  to  retain  it  for  their 
growth  is  seen  in  the  highest  degree  in  the  muscles.  Caspari 3  studied  a  dog 
that,  with  a  certain  diet,  was  in  ^equilibrium,  yet,  with  precisely  the  same 
food,  continuous  X-accumulation  occurred  when  the  dog  was  daily  subjected 
to  considerable  muscular  exertion.  Bornstein  4  was  able  to  show  that  the 
accumulation  of  albumin  attained  by  him  with  the  addition  of  a  larger 
amount  of  albumin  to  an  already  sufficient  diet  could  even  be  increased  by 
daily  muscular  exercise  in  moderation  (without  work  about  16  per  cent,  of 
what  is  ingested  is  accumulated;  with  moderate  labor  about  22  per  cent.).  He 
therefore  speaks  of  a  true  labor  hypertrophy  of  the  muscles,  and  the  investi- 
gations in  metabolism  carried  out  upon  a  large  scale  by  Atwater  and  Bene- 
dict 5  confirm  this  view.  Without  increasing  the  nitrogenous  food  of  their 
experimental  persons  during  the  period  of  labor,  they  produced  an  accumu- 
lation in  albumin  (in  contrast  to  an  N-loss  in  the  period  of  rest),  although  in 
the  period  of  labor  the  additional  calories  were  given  wholly  in  the  form  of 
carbohydrates  without  any  additional  albumin. 

It  is  of  course  obvious  that  this  labor  hypertrophy  has  its  limits.  Even 
with  continuous  muscular  work,  an  increase  of  albumin  in  the  food,  which 
is  also  limited  by  the  person's  digestive  capacity,  will  not  force  a  continuous 
accumulation  of  muscle.  A  condition  of  equilibrium  is  attained  in  which, 
however,  the  body  now  controls  more  organic  working  albumin  than  formerly, 
and  possesses  increased  vitality. 

For  the  treatment  of  the  cases  (constantly  multiplying  in  our  time)  in 
which  diminished  capacity  for  Avork  is  one  of  the  most  prominent  symptoms, 
these  new  studies  in  metabolism  contain  the  most  valuable  hints.  For  who 
will  maintain  that  every  patient  who  comes  to  us  with  a  body-weight  corre- 
sponding to  his  age  and  his  size  controls  an  amount  of  the  organic  substances 
used  in  metabolism  which  corresponds  to  his  maximum  or  even  to  his 
optimum  ? 

With  the  recognition  that  we  can  build  flesh  by  the  simple  addition  of 
albumin  to  the  food  (a  point  on  which  Pfliiger's  views  and  Voit's  teachings 

i  Lichtenfeldt,  "  Ueber  d.  Nährstoffbedarf  b.  Training."  Pfliiger's  Arch.,  Bd.  kwvi, 
p.  177. 

a  Pfliiger's  Arch.  f.  d.  ges.  Physiol.,  Bd.  li.  p.  310. 

•'■  Caspari,  "Ueber  Eiweissumsatz  und  Ansatz  bei  Muskelarbeit,"  Pßiiger's  Arch., 
Bd.  lx.x.xiii.  p.  6509. 

*Bornstein,  "  Eiweissmast  und  Muskelarbeit."     Pfliiger's  Arch..  Bd.  lxxxv,  iii.  p.  540. 

b Atwater  and  Benedict,  "Experiments  on  the  metabolism  of  matter  and  energy 
in  the  human  body."     Washington,  1899.     Quoted  by  Caspari,  lue.  cit.,  p.  539. 


THE  FOOD  REQUIREMENT   OF  THE  SICK  21 

are  sharply  contrasted),  the  saving  of  albumin  by  a  superfluous  calory  addi- 
tion is  not  divested  of  its  therapeutic  importance.  Where  a  simultaneous 
accumulation  of  fat  is  not  undesirable,  this  high  calory  diet  will,  as  a  rule, 
be  the  easiest  way  of  accumulating  albumin.  But  here  we  should  always 
remember  that  musculaT  work  is  ;in  important  auxiliary  means  of  fixing  the 
retained  albumin  in  the  organs  of  the  body,  and  that  a  simultaneous  high- 
proteid  diet  is  not  superfluous  or  even  unnecessary.  (See  the  considerable 
albumin  accumulation  in  the  investigations  of  Lüthje.) 

That  it  is  not  immaterial  in  saving  albumin  whether  the  calory  surplus  is 
brought  about  by  fat  or  carbohydrates  in  the  food  was  shown  long  ago  by 
the  investigations  of  Voit  and  Kühner.  Clinical  researches  in  metabolism 
have  confirmed  this.  In  Kayser's  '  researches  albumin  was  lost  when  he 
replaced  the  carbohydrates  by  an  isodynamic  amount  of  fat,  and  Tallquist2 
also  demonstrated  that  the  carbohydrates  were  capable  in  a  higher  degree  than 
fat  of  protecting  the  albumin  of  the  body  from  loss. 

To  understand  these  differences,  which  apparently  cannot  be  reconciled 
with  the  laws  of  isodynamics,  it  is  well  to  remember  the  experiments  of  Rubner, 
according  to  which  the  differenl  food  stuffs  (in  equal  excess)  increase  the 
interchange  of  energy  xcry  differently  because  they  are  utilized  in  unite  vary- 
ing amount-,  the  fat-  undergoing  combustion  in  metabolism,  less  so  than  the 
carbohydrates. 

In  the  practical  therapy  of  nutrition  this  preponderance  of  the  carbo- 
hydrates in  comparison  with  the  fats  as  albumin  savers  mus1  not  permit  us 
to  abstain  from  the  plentiful  use  of  fat  for  the  purpose  of  saving  albumin, 
especially  in  those  cases  in  which  carbohydrates  are  not  allowed,  i.e..  in 
diabetes.  And  since  we  see  here  that  with  an  exclusive  albumin  fat  diet 
(without  immoderate  excess  of  albumin)  diabetics  are  able  to  preserve  their 
albumin  condition  with  a  relatively  slight  administration  of  fat  calories,  we 
might  almost  believe  that  the  fat-  under  certain  circumstances  may  almost 
equal  the  carbohydrates  in  their  albumin-saving  effect.  In  the  very  plentiful 
use  made  of  fat  in  modern  dietetics  we  see  further  evidence  of  this. 


THE    FOOD    REQUIREMENT    OF    THE    SICK 

For  all  physician-  a  fair  comprehension  of  the  total  food  requirement  of 
the  diseased  organism  is  the  best  foundation  in  prescribing  a  suitable  diet. 
Modern  nutritive  therapy  no  longer  limit-  it-elf  to  the  prohibition  of  this  ot 
that  food,  it  expresses  positive  opinion-  in  ordering  the  diet,  both  ;i-  regards 
the  nature  and  the  quantity  of  the  food. 

Only  in  diseases  which  run  a  rapid  course  may  the  amount  of  food  con- 
sumed   he    \'nv    the    t  i  I  lie  ,  |  I  -  [V_'a  P  li  !<  I .        Hefe    real    -taiWathUI    I)  I :  I  \     lie    l|.rr--ar\    OH 

i  Kayaer,  "  Ueber  die  Beziehungen  von  Fetl  und  Kohlehydraten  cum  Eiweissumsate 
il.-s  Menschen."     Diu.,  Berlin,  1893. 

»Tallquist,  "Zur  Frage  dee  Einflusses  von  Fett  und  Kohlehydraten  au!  den  Eiweisa- 
Umsatz  des  Menschen."    Arch.  f.  Hygiene,  Bd.  \li.  |>-  177. 


22  ANALYSIS  OF   DISTURBANCES  OF  METABOLISM 

account  of  the  altered  functions  of  the  stomach  and  intestines,  and  we  may 
make  up  our  minds  regarding  the  quantity  and  choice  of  the  food,  quite  inde- 
pendently of  the  actual  food  requirements  of  the  body. 

In  convalescence  from  such  maladies  and  in  all  protracted  diseases,  how- 
ever, the  quantity  of  the  food  is  important.  A  proper  appreciation  of  this 
in  the  dietetic  treatment  of  chronic  diseases  will  give  the  physician  his  best 
results. 

The  appetite  which  normally  regulates  the  quantity  of  nourishment  in- 
gested, so  that  metabolism  is  always  exactly  covered  in  spite  of  all  variations 
in  regard  to  amount,  is  no  measure  for  the  amount  of  food  required  by  the 
sick.  Appetite  is  no  guide  when  wasting  diseases  increase  the  food  require- 
ment of  the  body;  appetite  is  equally  deceptive  when  excessive  corpulence 
makes  it  imperative  to  bring  about  a  reduction  of  the  body-weight. 

Only  an  exact  knoiuledge  of  the  amount  of  total  energy  metabolism,  the 
sum  of  the  energy  which  the  body  requires  and  utilizes  in  the  special  case, 
is  a  guide  to  the  physician  for  his  dietetic  orders  in  respect  to  quantity. 

THE   DEGREE   OF   OXIDATION 

Regarding  the  degree  of  metabolism  in  disease,  clinical  researches  in  the 
last  few  decades  have  given  us  definite  figures. 

Without  a  knowledge  of  the  amount  of  nourishment  consumed,  and  with- 
out a  proper  consideration  of  the  energy  values  contained  in  it,  mere  observa- 
tion at  the  bedside,  and  the  analysis  of  the  excretions  in  the  urine  exclusively, 
have  frequently  led  to  entirely  erroneous  conclusions.  French  literature  re- 
garding azoturia,  and  the  writings  of  Bouchard  regarding  the  slowing  of 
metabolism,  contain  numerous  examples  of  this  fallacy.  Increase  or  slowing 
of  metabolism  had  been  frequently  assumed  in  cases  in  which  later  control 
experiments  in  metabolism  proved  the  contrary.  When  the  exact  methods  of 
the  German  physiological  schools  (Voit,  Pflüger,  Zuntz)  were  employed  in 
the  analysis  of  the  processes  of  metabolism  in  the  diseased  organism  the  for- 
mer conclusions  were  reversed.  In  spite  of  this,  we  cannot  yet  claim  clear 
insight  into  many  pathologic  conditions,  but  we  may  nevertheless  say  that 
many  deeply  rooted  errors  have  been  corrected  by  the  methodic  quantitative 
labors  of  our  clinics. 

Metabolism  in  the  normal  human  adult,  in  complete  rest,  amounts  to 
about  one  calory  per  kilogram  of  body- weight  and  per  hour;  therefore  with  a 
weight  of  70  kilograms,  in  twenty-four  hours  it  is  1,680  calories  (=  21 
calories  per  kilogram).  Even  with  the  ordinary  exertion  of  daily  life  a 
decided  increase  occurs  (from  about  2,450  to  3,000  calories,  i.e.,  35  to  42 
calories  per  kilogram).  Increased  ingestion  of  food,  bodily  exercise  (muscu- 
lar labor)  and  the  unavoidable  giving  off  of  heat  while  exercising  arc  the 
factors  to  which  this  increase  of  transference  may  be  attributed.  The  amount, 
the  time  limits  and  duration  of  the  increase  of  metabolism  resulting  from 
exercise  in  healthy  persons  have  been  for  this  reason  closely  studied. 

The  hope  that  differences  in  the  rate  of  interchange  of  force  in  the  well 
and  the  sick  while  at  rest  could  be  measured  by  the  estimated  intensity  of 


THE   FOOD  REQUIREMENT  OF  THE  SICK  23 

oxidation  (0.  decomposition  and  C02  excretion)  which  characterizes  individ- 
ual pathologic  conditions  has  only  heen  fulfilled  to  a  slight  degree.  On  the 
other  hand,  later  researches  have  furnished  proofs  that  the  healthy  and  the 
sick  differ  in  the  reaction  of  their  organism  to  influences  that  increase  metab- 
olism (administration  of  food,  work  performed,  and  the  amount  of  heat 
given  off). 

To  appreciate  these  differences,  the  physiology  of  metabolism  must  be 
briefly  considered. 

The  increase  of  the  processes  of  oxidation  and  of  heat  production,  under 
the  influence  of  the  intake  of  nourishment,  which  may  be  subjectively  noted 
in  a  certain  feeling  of  warmth,  has  been  directly  measured  by  calorimetry. 
The  factors  of  the  respiratory  metabolism  have  also  been  indirectly  con- 
trolled. 

If  a  dog's  food  is  increased  upon  three  different  days  to  55  per  cent, 
above  its  previously  determined  calory  requirement  by  administering  iso- 
dynamic  amounts  of  albumin,  fat  and  carbohydrates,  its  elimination  of  heat 
upon  the  albumin  day  rises  19.7  per  cent.,  upon  the  fat  day  6.8  per  cent., 
and  upon  the  carbohydrate  day  10.2  per  cent.  (Rubner). 

This  coincides  exactly  with  the  figures  which  Magnus-Levy1  obtained  in 
In-  numerous  analyses  of  the  interchange  of  gases  after  the  administration 
of  particular  foods;  he  has  referred  to  these  in  his  valuable  dissertation  on 
the  influence  of  nourishment  upon  respiratory  metabolism.  He  also  deter- 
mined that  the  three  principal  food  products  increase  C02  excretion  and  0, 
consumption  in  \fvy  different  degrees.  The  proteids  again  take  the  first 
place;  they  increase  the  intensity  of  oxidation  from  50  to  60  per  cent.:  then 
follow  the  carbohydrates,  after  the  administration  of  which  the  interchange 
of  gases  is  only  increased  35  per  cent,  above  the  point  reached  when  the  stom- 
ach is  empty  ;  finally  the  fats,  which,  if  administered  in  amounts  that  do 
not  exceed  the  normal  requirement,  scarcely  increase  the  consumption  of  0, 
in  man  at  all,  and  in  the  <  1< >.lt  increase  it  only  about   H>  per  cent. 

Investigations  in  man  with  a  freely  chosen  diet  make  the  increase  of 
metabolism  after  a  men]  mtv  apparent.  In  the  firsi  four  hours  after  break- 
fast the  02  intake,  in  comparison  to  that  in  a  condition  of  rest,  is  increased 
'.'I.  37,  22  and  lit  percent.;  in  the  first  five  hours  after  the  midday  meal  36$, 
30,  20,  L8  and  L8  pel-  cent.,  and  in  the  first  three  hours  after  the  evening 
meal  ■'>'■'>.  31  and  is  per  cent.  According  to  this,  the  increase  of  the  inter- 
change "I'  gases  for  a  whole  day.  in  consequence  of  the  administration  of 
food,  amounts  to  L3  per  cent,  of  the  ( )_,  intake,  and  l!»',1  per  cent,  of  the  ('<)_, 
excretion. 

Eösslin  found  similar  figures  winch  are  the  basis  of  Vbitfs  investigations 

in  metabolism,  and  if  the  body's  requirement  does  nut  decidedly  exc 1  the 

intake  of  nourishment,  we  are  generally  right  in  counting  about  l<>  per  cent. 
as  the  increase  of  the  oxidation  processes  due  to  this  cause  (Zuntz). 

That  this  increase  of  oxidation  is  due  principally  to  the  increased  labor 

i Magnus-Levy,  "Ueber  <  1  i « ■  Grösse  <!>■-  respiratorischen  Stoffwechsels  anter  dem 
Einflüsse  der  Nahrungsaufnahme."    Pflüger's  Arch.,  Bd.  I\.  p.   1. 


24  ANALYSIS  OF   DISTURBANCES  OF  METABOLISM 

of  digestion,  and  that  with  a  superabundant  nourishment  these  increases  in 
metabolism  can  be  pushed  still  further,  was  for  a  long  time  the  predominant 
view  (Zuntz  and  v.  Mering).  Yet  lately  authors  have  come  more  and  more 
to  the  conclusion  that  the  increase  in  the  labor  of  the  digestive  organs*  is  not 
sufficient  to  explain  the  heat  production  after  intake  of  nourishment.  Inves- 
tigations on  this  point  have  been  carried  on  in  patients,  and  have  shown 
that  the  increase  in  metabolism  produced  by  the .  administration  of  food 
is  very  much  greater  in  some  individuals  than  in  others.  These  results  have 
increased  our  doubts  regarding  the  correctness  of  this  prevalent  opinion  (see 
below). 

Physiologists  have  determined  the  increase  of  metabolism  after  physical 
exertion  even  more  minutely  than  that  following  the  introduction  of  food. 

The  promptness  and  delicacy  of  the  changes  in  the  amount  of  oxidation 
after  muscular  labor  are  almost  astonishing. 

Increase  in  the  peristalsis  of  the  smooth  musculature  of  the  intestine 
after  the  introduction  of  mineral  salts  and  after  the  administration  of  food, 
changes  of  the  mechanism  of  respiration,  unconscious  muscular  effort  in 
strained  positions  of  the  body  or  when  the  temperature  of  the  skin  is  reduced, 
all  of  these  factors  influence  very  notably  the  interchange  of  gases.  Of  course 
a  much  more  striking  variation  becomes  apparent  in  tests  with  muscular  activ- 
ity of  a  type  which  can  be  mechanically  measured. 

Regarding  the  degree  to  which  the  process  of  oxidation  may  be  increased, 
when  the  amount  of  work  is  increased,  Zuntz  and  Katzenstein  have  given  us 
exact  figures.  It  is  an  absolute  law  that  02  consumption  and  CO,  formation 
increase  with  the  amount  of  muscular  labor.  Accordingly,  the  interchange 
of  gases  is  greater  when  the  individual  is  standing  than  when  he  is  in  the 
recumbent  posture.  The  increase  is  slight  if  the  person  is  standing  in  a  com- 
fortable position ;  it  amounts  to  about  20  per  cent,  of  the  "  rest  value  "  if 
the  person  is  standing  erect  as  in  military  drill. 

In  walking  the  consumption  of  products  becomes  from  2  to  4  times  as 
great,  according  to  the  rapidity  of  the  pace;  in  rapid  hill  climbing  it  is  5 
times  as  great  as  the  normal,  and  even  more. 

Proportionally  to  the  interchange  of  gases  the  heat  production  is  increased 
by  work  (in  comparison  to  rest  values),  as  Atwater  and  Benedict  have  deter- 
mined by  direct  calorimetry.  About  two-thirds  of  the  energy  set  free  by 
increased  decomposition  is  utilized  in  heat  production,  and  under  ordinary 
circumstances  only  one-third  in  mechanical  work.  (Under  the  influence  of 
practice  the  utilization  of  energy  for  the  performance  of  labor  may  increase 
just  as  it  diminishes  under  the  influence  of  exhaustion.) 

These  are  the  values  which  have  been  estimated  in  the  healthy.  As  to 
the  way  in  which  labor  increases  the  total  metabolism  in  disease,  and  how 
much  useful  energy  in  the  shape  of  chemical  activity  the  diseased  body  gets 
from  the  increased  decomposition  and  from  the  utilization  of  its  own  muscles, 
only  very  isolated  reports  are  at  hand. 

From  the  reply  to  these  questions,  conclusions  in  regard  to  pathologic 
metabolism  will  inevitably  result. 


THE  FOOD  REQUIREMENT   OF  THE  SICK  25 

The  question  most  discussed  has  been  whether  the  effects  of  cold  and 
heat  decidedly  increase  the  processes  of  combustion  in  the  body.  That  remain- 
ing in  a  cold  atmosphere  produces  a  great  loss  of  heat  will  scarcely  be  doubted, 
and  in  the  endeavor  of  the  body  to  maintain  its  own  temperature  a  decided 
loss  in  heat  in  consequence  of  cooling  cannot  be  prevented,  at  any  rate  not 
without  an  increased  consumption  of  its  combustible  material.  The  ques- 
tion to  be  chiefly  considered  is,  whether  the  irritation  of  cold  upon  the  sur- 
face of  the  body  produces  chemical  changes  in  the  interior,  and  thus  directly 
increases  the  intensity  of  combustion.  Speck  disputes  this,  and  considers 
that  some  physical  regulation  is  responsible  for  the  preservation  of  body  tem- 
perature by  limiting  the  Loss  of  heal  to  the  slightest  amount.  In  his  opinion, 
the  involuntary  muscular  contractions  which  result  as  the  effect  of  cold  are 
the  cause  of  the  increase  in  the  interchange  of  gases  which  has  been  observed. 

As  a  matter  of  fact,  Loewy,1  in  his  investigations  of  the  influence  of  cold 
upon  the  respiratory  metabolism,  was  unable  to  determine  an  increase  of  02 
consumption  in  all  cases  of  intelligent  persons  who  understood  their  bodily 
functions  and  who  maintained  completely  flaccid  muscles  during  the  investi- 
gations. This  corresponds  with  the  experience  of  Wolpert.  which  is  of  prac- 
tical importance,  thai  "  the  temperature  of  the  air  of  the  work-room,  «luring 
work  within  the  limits  of  5°  C.  and  25°  C,  exerts  no  especial  influence  upon 
the  degree  of  C02  excretion,  either  during  resl  or  during  strenuous  corporeal 
labor."  (In  contrast  to  this  are  the  views  of  Liebermeister,  according  to 
whom  the  beat  loss  from  the  effect  of  cold  causes  directly  an  increase  of  heat 
production.) 

I;  yarding  the  increase  of  oxidation  processes  which  are  generated  by  the 
action  of  beat  upon  the  body,  when  the  conduction  of  beat  by  evaporation  is 
prevented,  we  have  some  interesting  figures  obtained  in  the  experiments  on 
the  respiratory  metabolism  which  v.  Mering  had  performed  in  his  clinic  by 
Winternitz,2  Lohse,8  and  other-.  In  contrasl  to  the  decided  increase  of  oxida- 
tion produced  by  the  Hot-water  bath,  as  shown  by  these  investigations,  the 
effeel  of  a  hot-air  bath  upon  metabolism  is  quite  insignificanl  in  consequence 
of  a  prompt  physical  regulation  (sweating)  (Salomon).4 

According  to  the  few  researches  at  hand  (Schattenfroh,8  Wolpert')  we 
may  assume  that  the  influence  of  heat  and  cold  m  the  metabolism  of  the  sick 
is  quite  different  from  that  in  the  healthy.     In  the  obese,  for  example,  at  leasl 

'  .1.  Loewy,  "  Ueber  <l<-n  Einfluss  der  Abkühlung  auf  den  Gaswechsel  des  Menschen." 
Pfiüger'a  Arch.,  Bd.  xlvi,  p.  L89. 

-  //.  Winternitz,  "  Ueber  den  Einfluss  heisser  Bäder  auf  den  respiratorischen  Stoff- 
wechsel." Klin.  Jahrbuch,  1899,  Bd.  vii. — "Ueber  die  Wirkung  verschiedener  Bäder 
auf  den  Gaswechsel."    Hab.-Schrift,  1902,  Nauenburg. 

*  höhne,  "Ein  Beitrag  zur  Lehre  von  der  Einwirkung  des  beissen  Bades  auf  den 
menschlichen  Stoffwechsel."     Dias.,  Halle,  1900. 

i  Salomon,  "Ueber  'li.'  Wirkung  der  Heissluftbäder  und  elektrischen  Lichtbäder." 
Zeit  sehr.  f.  diät.  u.  physik.  Therap.,  Bd.  \.  Hefl  •'!. 

s  Schattenfroh,    "Respirationsversuche   an    einer    fetten    Versuchsperson."    Arch.    /'. 

//.'/.'/.,   Bd.   \\\\  iii.  p.  !»:!. 

■•  Wolpert  und  Broden,  "Respiratorische  Arbeitsversuche  bei  wechselnder  Luft 
feuchtigkeit  an  einer  fetten  Versuchsperson."    Arch.  f.  //.'/.</..  Bd.  \xxi\.  p.  298, 


26  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

under  certain  circumstances,  the  regulation  is  quite  different  from  that  in  the 
lean  person.  In  the  latter,  the  greatly  increased  heat  produced  by  hard 
physical  exercise  may  be  completely  removed  by  radiation  and  conduction; 
in  other  words,  by  increasing  the  temperature  of  the  skin,  and  this  is  attained 
by  increased  activity  of  the  circulation  of  the  blood.  In  the  obese  this  method 
is  unavailing,  and  the  secretion  of  sweat  must  vicariously  take  the  place  of 
the  insufficiently  active  blood-current.  Even  in  rest  and  in  sleep,  the  obese 
person,  particularly  in  a  very  warm  atmosphere,  throws  off  more  moisture  in 
a  humid  atmosphere  than  in  a  dry  one.  As  regards  the  endurance  of  high 
temperatures  the  person  with  great  deposits  of  adipose  tissue  is  easily  over- 
come, even  in  rest,  and  especially  so  on  exertion.  Besides  the  insensible  per- 
spiration which  must  be  counted  in  heat  regulation,  the  obese  loses  greatly 
by  the  sensible  perspiration  which  exudes  from  the  skin,  and  there  is  no  doubt 
that  as  a  result  of  this  his  metabolism  (through  changes  in  the  blood  com- 
position) is  very  different  from  that  of  the  lean  individual  when  exposed  to 
changes  of  temperature. 

The  numerous  and  practical  methods  given  us  by  physiology  for  estimat- 
ing the  degree  of  oxidation  in  health  make  it  obvious  that  pathologic  condi- 
tions should  be  studied  and  classified  from  the  same  point  of  view:  Is  the 
intensity  of  the  processes  of  combustion  increased  or  diminished,  or  unaltered  ? 

It  is  well  known  that  Bouchard  1  has  described  an  important  group  of 
diseases  (diabetes,  obesity,  gout)  as  the  consequence  of  a  "  slowing  of  metabo- 
lism," and  lately  has  extended  the  scope  of  this  disturbance  of  metabolism 
still  further  so  as  to  include  in  this  group  other  pathological  conditions. 

Formerly  such  facts  as  the  increased  excretion  in  the  urine  of  incomplete 
products  of  combustion  (uric  acid,  oxalic  acid),  maintenance  of  life  on  a 
lessened  amount  of  food,  the  deposition  of  fat  with  a  normal  intake  of  food, 
decrease  of  body  temperature  at  rest,  etc.,  led  him  to  ascribe  the  condition 
to  a  slowing  of  metabolism.  To-day  he  attributes  to  a  "  slowing  of  metabo- 
lism "  any  disease  which  is  shown  by  statistics  to  occur  frequently  in  asso- 
ciation with  diabetes,  obesity,  or  gout,  or  which  he  supposes  to  have  a  genetic 
relationship  with  these  diseases. 

Such  a  division,  justified  perhaps  from  the  standpoint  of  clinical  inves- 
tigation, has  absolutely  no  foundation  in  exact  quantitative  analyses  of  metabo- 
lism. Where  exact  analyses  have  been  carried  out  we  find  diseases  grouped  in 
an  entirely  different  manner.  In  quite  a  number  of  pathological  conditions 
which  are  to  be  considered  here,  we  have  exact  analytic  data  concerning  the 
intensity  of  the  processes  of  oxidation  and  it  will  be  interesting  to  consider  the 
results  from  this  standpoint. 

i  Bouchard,  "  Troubles  prealables  de  la  nutrition  in  Traite  de  Pathologie  generale," 
Tome  iii,  p.  179. 


THE  FOOD   REQUIREMENT  OF  THE  SICK 


27 


In  the  following  table,  the  "rest  values"  for  0,  consumption  and   CO., 
excretion,  in  various  diseases,  have  been  compiled. 


Disease. 

0, 

per  nun. 
c.c. 

co2 

per  min. 
c.c. 

Respir. 
Quotient. 

Author. 

Fasting  and  Rust  Value: 

Healthy  Individuals  {  Jjj111  ■  ■ 

3.27 

4.41 

2.38 
3.47 

/  Qeppert,     Arch.     f.     exp. 
\      Pathol.,  Bd.  xxii,  p.  367. 

Healthy  Individuals -[  ^r!'"'"-  '  ' 

5.21 

2.31 
3.04 

/  Ka  t z en  8 / e  i  n,      Pfliiger's 

j      Arch.,  Bd.  xlix. 

Healthy  Individuals  j  ^J'^""- '  ' 

3.68 
4.40 

3.18 
3.68 

j  Km  us,    Zeitschr.     f.     klin. 
Med..  Bd.  xviii.  p.  21. 

Health v   Man   (average   from  ) 
41   trials) \ 

3.89 

2.98 

0.766 

Minimis-  Levy,      Pfliiger's 
\      Arch.,  Bd.  lv,  p.  23. 

6.64 

5.45 

.821 

5.31 

4.25 

.799 

4.33 

3.4 

.783 

Very  severe  case 

6.80 

4.68 

.687 

Magnus-Levy,    Zeitschr.  f. 
klin.  Med.,  xxxiii,  p.  294 

6.  sf< 

•") .  *•_> 

845 

5.55 

4.65 

!838 

6.43 

4.84 

.754 

5.24 

4.09 

.783     . 

Graves'  Disease,  26  years  (4  trials). 

5.70 
5.41 

4.56 

3.81 

.7!» 
.70 

(  Stüve,  Art),  aus.  d.  St.  Kran- 
-j     kenhaus  Frankfurt  a.  M., 

Before    Thyreoid-Gland    Feed-  ) 
ing,  124  kilograms f 

(      1896,  p.  47. 

2.31 

1.74 

.75      j  Thieh  a.  NehHng,  Zeitschr. 

During  Thyreoid-Gland  Feeding. 

2.70 

1.98 

;;!       \      f.  klin.  Med.,  x'xx.  p.  47. 

Before  Thyreoid-Gland  Feeding.. 

During  Thyreoid-Gland  Feeding. 

3.82 
4.63 

3.20 
3.66 

!82 

.79 

'  Stüve,  loc.  cit.,  p.  45. 

Myxedema 

2.9 
5.4 

2.5 
3.8 

.86 

.74 

(  Magnus-Levy,     Deut  scb. 

After  Thyreoid-Gland  Feeding. 

\     med.  Wbchenschr.,   1896, 
i      i).  492. 

4.85 
4.5!) 

3.82 
3.6 

.786    F*air5iZrat«,Zeitschr.f.klin. 
.784    Fall  61     Med.,  xviii.  p.  177. 

Second  Week  of  Enteric  Fever. .. 

6.25 

5.07 

.812    Fall  2. 

Pneumonia  (inc.) .. . 

5.27 

4.84 

.919    Fall  3. 

Enteric  Fever : 

8.  \.  89.6° 

6.0 

4.7 

3.6 
8.2 

::::: 

1 

Erysipelas,  Fac. : 

5.5 

4.0 



7.  II.  89.8° 

;.:; 

4.4 



Phthisis,  Pulm. : 

!).  V.  89.2° 

6.8 
5.9 

4.7 
B.8 



Enteric  Fever : 

Riethus,  p.  240. 

5.9 

8.0 

1.6 

8.1 

Pneumonia : 

88.  VIII.  36.F 

5.5 

3.8 

Tub.  Pulm.: 

6.2 

5.8 

'•■:   VIII.  87.2 

5.9 

1.9 

Enteric  Fever  Convalescence  : 

4t  h  1  »av  "f  i  'onvalesoence 

1.40 

i.ni 

.758 

18th  1  >ay  of  1  lonvalescence 

1.90 

8.92 

.8 

5.86 

5.69 

.97 

Enteric  Fever  <  !om  alesoenoe : 

Sr,  nsiiii.  Zeitschr.   f.   klin. 

i::tli  Day  of  1  lonvalescence 

1  88 

Bied.,  \\w  i.  p.  '.i I. 

86th  Day  of  1  lonvalescence  .... 

5.05 

1  :; 

.84 

Pneumonia-Convalescence  i 

4.88 

3.68 

.85 

28 


ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 


Disease. 


Diabetes : 

1.  Severe  case 

2.  Very  severe  case 

3.  Very  severe  case 

4.  Mild  case 

,5.  Mild  case 

6.  Mild  case 

Diabetes 

Severe  case 

Severe  case 

(Nine -hour  investigation   with] 

i/o/j/je-jSey/er's  respiration-ap- 
paratus with  simultaneous  ad- 
ministration  of   food  during  | 

the  investigation.) J 

Anemia,  pernio,  progress 

Chlorosis 

Chlorosis 

Secondary   Anemia   after   hemor- 
rhage from  hemorrhoids 

Chlorosis 

Chlorosis 

Chlorosis 

Secondary  Anemia 

Pernicious  Anemia 

Severe  Anemia 

Same  patient  with  continued  im- 
provement  

Obesity : 

Dr.  Dr.  Gew.,  94  kilograms 

Frl.  N.,  70  kilograms 

Fr.  Mai.,  69.5  kilograms 

Fr.  St.,  76  kilograms 

Frl.  E.  Kr.,  77  kilograms 

Fr.  Kr.,  88  kilograms 

Frl.  Bu.,  107  kilograms 

Fr.  Ha.,  111.4  kilograms 

Fr.  Schu.,  133.3  kilograms 

Hr.  A.  S.,  80.2  kilograms 

Hr.  Mar.,  80  kilograms 

Hr.  Stab.,  91.5  kilograms 

Hr.  Dr.  Da.,  92.7  kilograms 

Hr.  Ha.,  96  kilograms 

Hr.  D.  0.,  109  kilograms 

Fr.  Eckmann 

D.  P 

Aged: 

Fr.  Kr.,  75  years 

Fr.  Kl.,  71  years 

Hr.  A.  Kr.,  71  years 

Hr.  J.  K.,  78  years 

Youth  : 

Boy,  24  years,  11.5  kilograms. .  . 

Girl,  6^  years,  18.2  kilograms. . . 

Girl,  20  years,  61  kilograms 


per  min. 
c.c. 


C02 
per  min. 


Respir. 
Quotient. 


4.06 
4.54 
3.99 
3.05 
3.04 
3.51 
3.96 
6.23 
5.164 


5.744 


4.53 
5.11 
5.48 

4.58 
3.47 
3.15 
3.38 
4.18 
4.15 
4.26 

3.83 

2.71 
3.33 
3.45 

2.48 
2.94 
3.74 

2.40 

2.88 

2.12 

3.22 

3.48 

2.82 

2.83 

2.41 

2.82 

2.7 

2.8 

4.25 
3.16 
3.42 
2.61 

9.76 
7.42 
3.56 


3.14 
2.97 
2.71 
2.66 
2.31 
2.73 
2.93 
•4.425 
3.795 


3.65 


3.22 

3.7 

4.0 

3.45 
2.96 
2.92 
3.29 
3.58 
2.94 
3.6 

3.35 

1.95 
2.34 
2.77 
1.87 
2.39 
2.39 
1.85 
2.31 
1.52 
2.42 
2.83 
2.04 
2.32 
1.87 
2.37 
1.98 
2.26 

3.36 
2.55 

2.70 
2.61 

8.16 
6.04 
2.90 


.77 

.66 

.68 

.73 

.76 

.78 

.74 

.7 

.617 


.64 

71 

72 

727 

75 
85 
92 
975 

86 
70 


804 
756 
812 
637 

771 

802 

719 

750 

814 

721 

821 

777 

840 

74 

81 

768 
807 
79 
725 

84 
81 

82 


I  Leo,  Zeitschr.  f.  klin.  Med., 
f     Bd.  xix,  p.  117. 

Stüve,  loc.  cit ,  p.  49. 

Weintraud  und  Laves,  Zeit- 
schr. f.  phys.  Chem.,  Bd. 
xix,  rieft  6. 


1 

[  Fr.  Kraus,  Zeitschr.  f.  klin. 
Med.,  xxii,  p.  49. 

)  Thiele  u.  Nehrinq, Zeitschr., 
-  f.  klin.  Med.,  Bd.  xxx,  p. 
)      56. 

;  Thiele  u.  Neliring,  loc.  cit., 
f      p.  59. 

i  Magnus- Levy,  Berliner  klin. 
Wochschr.,  1895,  p.  351. 

\  v.  Noorden,  Lehrbuch,  p. 
>      448. 


Magnus- Levy,  Zeitschrift  f. 
klin.  Med.,  xxxiii,  p.  302. 


77/  iele  u.  Nehring,  loc.  cit. 
Stüve,  loc.  cit.,  p.  46. 


Magnus-Levy,  Zeitschrift  f. 
klin.  Med.,  xxxiii,  p.  266. 


Magnus-Levy,  Berlin,  klin. 
Wochschr.,  1895,  p.  652. 


Among  pathological  conditions  in  which  investigation  of  the  respiratory 
metabolism  has  invariably  shown  an  increase,  Graves'  disease  occupies  the 
first  place. 


THE  FOOD  REQUIREMENT  OF  THE  SICK  29 

Magnus-Levy,1  by  his  many  valuable  physiological  researches  in  this  realm, 
was  the  first  to  attempt  to  estimate  the  factors  of  respiratory  metabolism  in 
Graves'  disease  (Basedow's  disease).  He  found  the  02  intake  and  the  ( "'<>_ 
excretion  decidedly  greater,  even  50  per  cent,  greater,  than  the  rest  values  of 
healthy  individuals.  At  the  same  time  his  results  showed  that  the  admin- 
istration of  thyreoid  extract  in  normal  person-  resulted  in  the  same  increase 
of  the  interchange  of  gases. 

These  investigations  also  furnished  the  first  experimental  proof  that  there 
are  toxins  in  metabolism  which  cause  increased  activity  in  the  cells  of  the 
body  during  rest,  and  tin's  discovery  furnished  a  clue  for  the  understanding  of 
the  disturbance  in  metabolism  observed  in  Graves'  disease  (emaciation,  sweat- 
ing, sensations  of  heat)  as  well  as  the  clinical  symptoms  after  thyreoid  -land 
feeding,  which  are  in  many  points  similar. 

A  year  before  this  practical  use  had  been  made  of  the  effect-  of  metabolism 
thus  elucidated,  when  Leichtenstern  -  determined  the  actual  loss  in  weight  of 
obese  persons  after  thyreoid  gland  administration,  and  with  this  inaugurated 
a  medical  treatment  for  obesity. 

The  quantitative  investigations  in  metabolism  which  followed  the  clinical 
advice  of  Leichtenstern.  the  loss  of  weight  after  thyreoid  administration,  and 
the  attempts  to  analyze  the  constituents  of  this  loss  first  demonstrated  that 
tlnre  is  a  decided  loss  in  proteids  and  water.  But  some  of  the  investigators' 
boob  observed  that,  even  when  N-eqw'librium  was  completely  maintained, 
there  was  decided  loss  in  weight  which  could  only  he  explained  by  loss  of  water 
and  fat.  Analysis  of  the  respiratory  metabolism  showed  an  enormous  increase 
in  the  intensity  of  the  processes  of  oxidation,  and  thus  confirmed  the  clinical 
observation  that  in  the  losses  of  weight  which  are  observed  during  thyreoid 
feeding  it  is  particularly  the  body  fat  which  i<  subjed  to  increased  oxidation. 

Bui  it  is  certainly  not  on  the  body  fai  alone  that  the  overflooding  of 
metabolism  with  thyreoid  Becretions  exerts  its  deleterious  action  in  severe  cases 
of  Graves'  disease. 

Even  if  we  take  the  largest  increase  over  "  resl  metabolism  "  which  has 
ever  been  observed  in  Graves'  disease  (about  "><>  per  cent,  ot  1,800  calories), 
an  additional  consumption  of  900  calories  or  aboul  inn  grams  of  fat  in  the 
daily  food  would  cover  the  loss.  Ye\  a-  a  matter  of  fact  exact  quantitative 
investigations  in  metabolism  have  shown  that  we  are  not  always  successful  in 
maintaining  the  equilibrium  of  body-weighl  (Fr.  Müller)/  even  by  a  very 
profuse  administration  of  nourishment,  and  only  in  mild  cases,  when  condi- 
tions are  favorable   for  a   profuse   intake  of  noiiri-dmieiit    (good   appetite),  can 

the  proteid  constituents  of  the  body  In-  preserved   (Scholz).'1 

The  etiolögic  relations  and  the  clinical  contrasts  between  Graves'  disease 

i  Vagnua-Levy.     Berl.  Hin.  Wochenachr.,  1895,  St.  '?0. 

t  Leichtenstern,  "Ueber  Myxödem  und  Boer  Entfettungscuren  mit  Schilddrüsenfül 
terung."     Deutsche  med.  Woohenachr.,  1894,  \>.  50. 

Orcuoitz,   Münchener  >>i.,i    Woohenachr.,  1806,  Nr.  14. 

*  Fr.   Miilh  r.    Irch.  /'.  I.lin.   M.il..  v.l.  li.  p 

b  Beholz,  Centralbl.  f.  inn.    !/../..  1895,  \r.    i:;. 


30  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

and  myxedema   (or  sporadic  cretinism)  make  it  advisable  to  include  these 
diseases  here. 

They  are  the  only  ones  in  which  a  diminution  of  the  normal  oxidation 
has  been  proven  with  certainty  to  be  intimately  connected  with  disease.  The 
values  which  Magnus-Levy  1  obtained  in  a  case  of  sporadic  cretinism  (for  02 
intake  2.8  to  3.0  c.c,  for  C02  excretion  2.4  to  2.5  c.c.,  per  kilogram  and 
per  minute)  are  near  the  lowest  normal  limits,  and  when  taken  in  connection 
with  the  clinical  symptoms  (low  temperature,  diminished  formation  of  sweat, 
inactivity  of  the  muscles)  the  few  analyses  of  metabolism  which  have  been 
made  justify  the  conclusion  that  in  this  instance  a  diminution  of  metabolism 
was  actually  present,  and  was  due  to  the  nature  of  the  disease. 

In  no  other  diseases  in  which  up  to  the  present  time  the  interchange  of 
gases  has  been  determined  is  the  explanation  of  the  results  obtained  so  simple 
and  clear  as  it  is  •  in  Graves'  disease  and  in  myxedema.  Nevertheless,  the 
figures  obtained  have  considerably  modified  the  prevailing  views  regarding 
the  intensity  of  the  processes  of  combustion  in  special  .diseases,  and  by  this 
means  have  broadened  our  insight  into  their  pathogenesis,  and  have  furnished 
us  much  help  regarding  their  treatment. 

For  a  long  time  it  was  supposed  that  in  fever  the  processes  of  oxidation 
were  increased.  Nothing  was  more  obvious  than  to  connect  the  higher  tem- 
perature of  the  body  with  an  increased  use  of  carbon-containing  material  in 
the  body. 

Regarding  the  degree  of  the  increase  of  oxidation  in  the  fever  of  human 
beings  experimental  investigations  in  animals  could  only  give  us  imperfect 
standards  (May-).  Researches  which  Kraus3  carried  out  in  febrile  human 
beings  have,  however,  shown  that  fever  is  possible  without  decided  increase 
of  the  oxidation  processes  (measured  according  to  Zuntz's  method  which  shows 
the  relation  of  the  factors  of  metabolism).  This  is  particularly  true  of  such 
individuals  as  have  had  fever  for  a  long  time — those  suffering  from  inanition 
(Robin  et  Binet4). 

In  acute  infectious  fevers,  the  02  consumption  amounts  to  scarcely  more 
than  20  per  cent,  above  the  normal.  Previous  to  this,  higher  values  have 
frequently  been  obtained  for  the  increase  in  oxidation,  but  this  has  been  due 
to  accidental  factors  such  as  greater  muscular  activity  owing  to  dyspnea, 
increased  muscular  tonus  in  the  chill  of  fever,  etc. 

The  amount  of  increase  in  the  interchange  of  gases,  which  Kraus  and 
Riethus  5  have  shown  to  be  attributable  to  some  febrile  infections,  is  suffi- 

i  Magnus-Levy,  Deutsche  med.  ^Yochenschr.,  1S06,  p.  401. 

2  May,  "  Der  Stoffwechsel  im  Fieber,"  "  Experimentalle  Untersuchungen."  Zeit- 
schrift f.  Mol.,  vol.  xxx,  p.  1. 

s  Kraus,  "Ueber  den  respiratorischen  Gasaustausch  im  Fieber."  Zeitschr.  f.  Min. 
Med.,  vol.  xviii,  p.   1G0. 

4  Robin  et  liinet,  "  Etudes  cliniques  sur  le  chemismc  respiratoire."  Arch,  gener.  de 
mid.,  1896,  Juin  et  Octobre. 

5  Riethus,  "  Beobachtungen  über  den  Gaswechsel  kranker  Menschen  und  den  Einfluss 
antipyretischer  Medicamente  auf  denselben."  Arch.  f.  exp.  Path.  u.  Pharm.,  vol.  xliv, 
p.  239. 


THE   FOOD   REQUIREMENT   OF   THE   SICK  31 

ciently  explained  by  the  increase  in  proteid  decomposition  which  forms  part 
of  every  febrile  process  and,  as  it  appears,  bears  a  much  more  intimate  rela- 
tion to  febrile  processes  than  the  increase  in  oxidation  (Traube.  Naunyn1). 

The  investigations  which  are  constantly  multiplying  make  it  obvious  that 
there  is  no  constant  and  direct  relation  between  the  height  of  the  temperature 
and  the  degree  of  the  increase  of  oxidation.  Febrile  conditions  occasionally 
show  a  conspicuously  low  consumption  of  oxygen,  and  afebrile  cases  con- 
spicuously high. 

The  indications  to  be  derived  from  this,  in  regard  to  the  regulation  of 
nutrition  in  fever  patients,  are  obvious.  It  is  not  the  absolute  height  of  the 
fever  which  endangers  the  metabolism  of  the  body,  and  for  this  reason  it 
should  not  be  our  only  care  to  study  minutely  the  diet  of  our  patients.  On 
the  contrary,  it  is  the  toxins  produced  by  infection  which  prove  injurious 
to  the  nutritive  condition  of  the  body,  and  in  all  cases  in  which  the  physician 
recognizes  these  deleterious  consequences,  he  must  arrange  the  dietary  accord- 
ingly. Remembering  this  he  will  not  disregard  the  dietetic  indications  of 
many  afebrile  infectious  diseases  (some  forms  of  pulmonary  tuberculosis). 

In  contrast  with  fever,  in  which  the  increased  combustion  causes  much 
less  difficulty  than  the  toxogenous  proteid  decomposition  (see  below)  is  the 
nutrition  of  convalescents.  Here  these  difficulties  are  usually  slight. 
Analysis  of  the  diet,  under  which  debilitated  patients  after  long-continued 
under-nutrition  are  able  to  increase  in  weight,  has  frequently  shown  aston- 
ishingly low  energy  values.  Vr.  Müller-  in  a  case  of  stenosis  of  the  esophagus 
after  intoxication  from  caustic  potadi  studied  a  fearfully  emaciated  patient, 
who  gained  3.5  kilograms  in  three  weeks,  under  a  diet  of  only  24.7  to  30 
calorie-  per  kilogram.  Among  <;.  Klemperer's8  patients  there  were  some 
who  throve  very  well  on  a  diet  containing  only  13.5  to  18  calories  per  kilo- 
gram. A  patient  of  Xebelthau's  '  who  was  greatly  emaciated  in  consequence 
of  stubborn  vomiting,  accumulated  very  considerable  amounts  of  albumin 
despite  a  quite  insufficient  proteid  and  calory  administration  after  she  had 
remained  for  four  days  without  any  food. 

Without  doubt  the  processes  of  oxidation  are  here  decreased  to  a  certain 
decree.  The  metabolism  is  diminished  to  the  minimum  which  is  absolutely 
necessary  to  maintain  life.  Correspondingly,  the  formation  of  heat  i-  alight 
(tendency  to  chilliness),  and  the  power  of  bodily  activity  is  limited. 

There  is  no  objection  to  our  assuming  that  this  diminution  of  metabolism 
in  chronic  under-nutrition  i-  a  true  slowing  of  metabolism.  This  makes  it 
possible  to  maintain  life  even  under  very  unfavorable  external  conditions. 
and  is  apparently  produced  gradually  by  adaptation  and  habit. 

Sudden  withdrawal  of  nourishment  does  not  diminish  th(   total  metabolism 

i  X ./ huhu.  Berliner  klin.  Wochenschr.,  L869,  \r.   ). 

-/';/'"/.  Hüller,  " Stoffwechseluntersuchungen  ron  Krebskranken."  Zeiteohr.  f.  hlin. 
Med.,  vol.  \\  i.  p.   196. 

'■<!.  Klemperer,  "Ueber  Stoffwechsel  und  Ernährung  in  Krankheiten."  Zeitschr.  f. 
hlin.    Med.,  vol.  w  i.  p,  550. 

>  Vebelthau,  "län  Beitrag  zur  Kenntnisa  der  A.cetonurie."  CentralbU  f.  inn.  I/.-/.. 
1897,  i».  !»77. 


32  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

to  anything  like  the  same  degree.  In  the  estimations  which  Zuntz  and  Leh- 
mann 1  carried  out  in  the  professional  faster  Cetti,  the  "  rest-values "  for 
02  consumption  and  C02  excretion  during  the  days  of  starvation  (on  the 
average  4.78  and  3.34  c.c.)  were  but  little  lower  than  during  the  days  pre- 
ceding the  fast  (5.35  c.c.  02,  and  3.90  c.c.  CO.,).  In  investigations  in  the 
case  of  the  faster  Breithaupt,  the  average  values  prior  to  the  fast  and  after 
it  had  begun  were  almost  exactly  the  same. 

Whether  the  ease  with  which  patients  convalescent  from  acute  febrile 
disease  compensate  for  their  loss  in  weight  depends  upon  the  same  capacity  to 
economize  in  metabolism  which  enables  patients  in  a  state  of  chronic  under- 
nutrition to  gain  weight  even  on  a  diet  of  low  calory  value  is  a  mooted  ques- 
tion. Svenson  2  has  recently  thrown  light  upon  this  question  by  investiga- 
tions of  metabolism  in  convalescence  from  pneumonia  and  from  enteric  fever. 

His  figures  (see  Table  on  page  27)  do  not  show  a  tendency  to  economy 
in  the  processes  of  combustion.  On  the  contrary,  in  the  first  afebrile  days 
after  a  severe  enteric  fever,  he  found  a  slight  diminution  of  the  respiratory 
values;  true  convalescence  with  increase  in  weight  was  being  characterized  by 
high  values,  and  metabolism  was  therefore  increased.  Hence  the  increase  in 
weight  cannot  be  explained  by  assuming  a  diminution  of  consumption.  On 
the  contrary,  the  balance  is  positive  because  the  intake  of  nourishment  with 
the  usual  increased  appetite  of  convalescence  is  decidedly  greater  than  the 
energy  value  of  the  average  food  of  maintenance  (60  to  90  calories  per  kilo- 
gram). 

The  "  rest-value "  for  metabolism  in  convalescence  then  is  in  any  case 
increased  and  this  is  particularly  true  of  the  metabolism  after  work,  as 
was  shown  bjr  Svenson's  further  researches.  The  convalescent  is  able  to 
utilize  in  muscular  work  only  a  small  portion  of  the  energy  set  free  by  the 
processes  of  combustion,  and  therefore  has  a  higher  C02  consumption  per 
kilogram  meter  than  the  healthy  man.  There  is  no  economy  of  metabolism 
here. 

Diabetes  mellitus  was  for  a  long  time  looked  upon  as  a  disease  in  which 
metabolism  was  increased.  The  enormous  ingestion  of  food  which,  because 
unsuitable,  is  often  insufficient  (in  spite  of  its  great  energy  value)  to  satisfy 
the  appetite  which  accompanies  diabetes  mellitus,  and  to  maintain  nutrition, 
naturally  led  to  this  view,  at  a  period  when  a  deeper  insight  into  the  econ- 
omy of  metabolism  of  the  diabetic  was  not  yet  possible. 

The  quantitative  analyses  of  metabolism  which,  because  of  therapeutic  ex- 
periments in  diet,  were  carried  out  especially  often  in  diabetics,  soon  showed, 
however,  that  with  suitable  food,  the  usual  calory  intake  was  sufficient  to 
maintain  the  equilibrium  of  metabolism  even  in  severe  diabetes. 

The  diabetic  perversion  of  metabolism  cannot  be  due  to  an  increased  inter- 
change of  products  since  it  is  possible  with  a  diet  which  contains  only  25 

1  Z«Bfe  und  Lehmann,   Virchow's  Arch.,  vol.  exxxi;   Suppl.-Heft,  pp.  50  und  91. 
z  Svenson,    "  Stoffwechselversuche    an    Roeonvalcscenten."      Zeitschr.   f.    klin.    Med., 
vol.  xliii.  p.  86. 


THE   FOOD  REQUIREMENT  OF  THE  SICK  33 

calories  per  kilogram  to  maintain  the  patient  for  weeks  in  an  active  con- 
dition.1 

On  the  contrary,  observation  proves  that  metabolism  in  the  diabetic  may 
occasionally  be  abnormally  slow,  and  the  experience  accumulated  by  many 
careful  investigations  of  the  nutrition  of  diabetics  demonstrates  that,  in  many 
cases,  it  is  in  fact  slower  than  the  metabolism  of  a  healthy  person.  I  say  in 
many  cases,  for  this  is  by  no  means  true  of  all.  A  pathologic  diminution  of  the 
nutritive  requirement  is  by  no  means  the  rule  in  diabetes.  If.  however,  we 
give  for  a  long  time  a  diet  which  is  apparently  superfluous  hut.  in  reality. 
quite  insullicient — because  improper — under  the  influence  of  this  chronic 
nnder-riutrition  the  same  diminution  in  metabolism  may  occur  that  also 
occurs  in  other  persons  who  are  under-nourished  (see  above).  I hin,'  it 
becomes  possible  to  support  life  on  less  food  than  is  necessary  for  healthy 
people  and  to  increase  the  diabetic's  weight  with  a  diet  which  is  only  just 
sutlieient  for  the  needs  of  a  normal  person. 

Correspondingly,  the  rest  values  for  0,  consumption  and  00,  excretion 
that  have  been  determined  in  diabetes  neither  exceed  nor  fall  below  the  limits 
which  we  have  come  to  recognize  in  the  normal  individual  (Voit  and  Petten- 
kofer,  Leo,2  Weintraud  and  Laves,"  Stiive4). 

The  same  is  proven  by  the  investigations  of  Magnus-Levy  in  gout,  which 
Bouchard,  as  is  well  known,  includes  with  diabetes  among  diseases  character- 
ized by  decreased  metabolism. 

In  the  various  forms  of  anemia  (chlorosis,  secondary  and  pernicious 
anemia)  we  might  expecl  diminution  of  ()_,  intake,  in  view  of  the  more  or 
less  marked  diminution  of  the  oxygen  carriers  in  the  blood,  especially  if  we 
remember  the  fatty  degeneration  of  organs,  which  is  frequently  observed  in 
anemia. 

Experimental  investigation,  however,  ha-  decided  against  this  view.  In- 
deed the  values  determined  for  02  intake  and  ('<)_,  output  have  1 n  shown 

to  he  near  the  upper  physiological  Hunts,  in  those  cases  of  pernicious  anemia 
which  are  characterized  by  increased  proteid  decomposition,  this  limit  has 
even  been  several  time- exceeded  (Meyer."'  Magnus-Levy ) .a  A  diminution  of 
metabolism  due  to  impoverished  blood  cannot  therefore  be  assumed  (Kraus,1 
Thiele  and    Nehrin 

i  Weintraud,  "Untersuchungen  liber  den  Stoffwechsel  im  Diabetes  melitus."  Bibl. 
med.,  Cassel,   ls:i:;. 

-  /.•'-.  "  Ueber  den  respiratorischen  Stoffwechsel  und  Diabetes."  Zeit  sehr.  f.  klin. 
Med.,  vol.  \i\. 

Weintraud   und    Laves,   "Ueber   den    respiratorischen    Stoffwechsel    im    Diabetes." 
Zeitschr.  f.  phys.  Chemie,  vol.  rix. 

•»  siiirc,  Arbeiten  aus  dem  Btädt.     Krankenhaus  Frankfurt  a.  M..  1806,  p,    19, 
'•  B.    Meyer,  "1  eher  0    Verbrauch  und  CO     Ausscheidung  bei  Anämien."     Dissert., 
Bonn,  1892. 

i  Magnus  Levy,  Berliner  klin.  Wochenschr.,  1895,  p.  3S1. 

r Kraus,  "Ueber  den   Binflusa  von   Krankheiten,  besonders  von  anfimischen  Zustün- 
den, auf  den  respiratorischen  Gaswechsel."     Zeitschr.  f.  klin.   Med.,  vol.  \\ü.  p.   149. 
■  Thiele  und   Weh/ring,  Zeitschr.  f.  klin.   Med.,  vol.  kxz. 
I 


34  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

It  is  remarkable  that  in  certain  forms  of  obesity  no  diminution  of  the 
physiologic  processes  of  combustion  can  be  determined.  Clinicians  have 
noted  two  classes  of  cases,  (a)  those  in  which  overeating  and  deficiency  of 
muscular  labor  were  the  obvious  causes  of  the  accumulation  of  fat,  and  (&) 
those  in  which  even  a  normal  amount  of  food  resulted  in  accumulation  of 
fat,  and  even  with  a  decided  diminution  of  nourishment  it  was  impossible  to 
bring  about  a  reduction  in  weight. 

v.  Noorden  1  reports  the  case  of  a  man  weighing  102  kilograms  who — in 
spite  of  the  fact  that  his  food  during  three  months  did  not  exceed  1,720 
calories  per  day,  and  that  as  an  inspector  of  a  country  district  he  had  every 
day  plenty  of  exercise — lost  only  a  kilogram  of  weight  in  three  months.  In 
a  lady  weighing  86  kilograms  he  failed  to  produce  the  slightest  diminution 
in  weight  in  the  course  of  six  weeks,  though  he  reduced  the  food  to  900  to 
1,000  calories.  In  a  woman  weighing  145  kilograms,  Stadelmann  2  reports 
that  with  a  diet  containing  but  1,500  calories  per  day  she  not  only  throve  but 
even  gained  one  kilogram  per  week  in  weight.  Only  when  nutrition  was 
reduced  to  1,000  calories  did  she  begin  to  lose  weight,  while  on  1,200  calories 
she  gained  in  weight  for  a  time.  (Compare  the  criticisms  of  these  reports 
in  Eubner.)3 

In  the  light  of  these  observations  the  question  constantly  arises,  whether 
the  tissue  elements  of  obese  persons  do  not  require  a  slighter  amount  of  mate- 
rial to  perform  their  normal  functions,  and  whether  the  very  ready  accumula- 
tion of  fat  is  not  due  to  the  fact  that  the  organs  function  more  economically 
than  under  normal  conditions,  v.  Noorden  was  the  first  to  study  this  ques- 
tion by  exact  experimental  investigation,  and  in  his  excellent  text-book,  The 
Pathology  of  Metabolism,  which  stimulated  so  many  later  researches  in  metab- 
olism, he  worked  out  in  two  cases  of  obesity  the  first  figures  representing  the 
consumption  of  oxygen  and  the  excretion  of  carbonic  acid.     (See  Table.) 

Eesearches  by  Magnus-Levy  followed  these  (Table).  All  the  "minute- 
kilo-values  "  taken  with  an  empty  stomach  are  low,  in  fact  near  the  lowest 
limit  of  the  normal  standard  figures.  "  But  they  are  not  so  low  that  a  dimin- 
ished oxidation  energy  of  the  cells  must  be  assumed,  especially  if  we  consider 
that  the  values  per  kilogram  as  calculated  in  the  obese  become  lower  the  more 
fat  the  body  accumulates.  But  in  metabolism  during  quiet  respiration  this 
factor  is  not  operative.  In  studies  regarding  the  intensity  of  the  process  of 
combustion  fat  cannot  be  looked  upon  as  of  the  same  value  as  flesh  and  gland 
substance"  (Magnus-Levy).  Thus  when  it  appeared  that  analysis  of  the 
respiratory  metabolism  (according  to  the  Zuntz-Greppert  method)  would  yield 
no  support  for  the  belief  that  there  is  a  diminution  of  the  processes  of  com- 
bustion in  the  obese,  new  researches  by  Jaquet 4  suggested  the  method  by 
which  in  the  corpulent  an  economy  of  the  food  material  introduced  produces 
the  gradual  deposition  of  fat. 

i  r.  Noorden,  "  Die  Fettsucht,"  in  Nothnagel's  Handbuch,  p.  31. 

2  Stadelmann,  Berliner  klin.  Wochensehr.,  1001,  Nr.  25. 

3  Rubner,  Beiträge  zur  "  Ernährung  im  Kindesalter,"  Berlin,   1902,  p.  31. 

4  Jaquet  und  Svenson,  "  Zur  Kenntniss  des  Stoffwechsels  fettsüchtiger  Personen." 
Zeitschr.  f.  klin.  Med.,  Bd.  xli,  p.  375. 


THE  FOOD   REQUIREMENT  OF  THE  SICK  35 

According  to  a  diagram  proposed  by  Magnus-Levy1  the  total  metabolism 
of  an  individual  may  be  considered  to  be  composed  of  three  factors : 

1.  The  entire  metabolism  in  rest  and  with  an  empty  stomach. 

2.  The  metabolism  which  is  necessary  to  sustain  the  work  (glandular  and 
intestinal)  that  results  in  the  assimilation  of  t 1  introduced. 

3.  The  metabolism  which  is  necessary  for  useful  or  useless  movements  of 
the  body. 

Metabolism  thus  estimated  amounts: 

For  1 to  1,600  calories. 

For  2 to      '240 

For  3 to     860       " 

Total 2.700 

In  fact  it  is  unlikely  that  an  obese  person  requires  less  energy  than  a 
healthy  person  for  the  maintenance  of  his  vital  functions,  for  normal  activity 
of  the  heart  and  respiration,  for  the  rest  metabolism  of  the  glandular  activity 
and  for  the  maintenance  of  body  heat.  v.  Noorden  mentioned  the  possibility 
that  for  3  he  saves  something,  because  the  development  of  heat  which  accom- 
panies physical  exercise  per  kilogram  of  working  protoplasm  and  per  kilo- 
gram-meter of  physical  exercise  is  less  in  him  than  in  the  average  person,  but 
Magnus-Levy  expressed  his  doubts  of  this.  It  was  therefore  particularly  in- 
teresting that  Jaquet  found  the  value  for  2  diminished  in  his  corpulent  patient. 
The  increase  of  the  products  of  combustion  due  to  ingestion  of  nourishment 
was  decidedly  less  and  of  shorter  duration  in  his  three  obese  patients  than 
in  normal  persons.  It  was  shown  that  during  a  period  of  digestion  reckoned 
as  fourteen  hours,  the  obese  require  21.84  liters  O,  less  than  a  normal  person 
under  similar  circumstances.  With  this  amount  of  02,  11  grams  of  tat  can 
be  burned,  and  a  daily  Baving  of  11  grams  of  fat  corresponds  to  an  accumula- 
tion of  I  kilograms  of  fat  a  year.  Thus  the  analysis  of  respiratory  metabolism 
opens  a  path  for  the  understanding  of  the  pathogenesis  of  constitutional 
obesity. 

Practical  rules  for  the  nutrition  of  the  sick  cannot  be  immediately  deduced 
from  these  clinical  studies  regarding  the  amount  of  respiratory  metabolism  in 
the  diseases  which  have  been  mentioned,  valuable  as  they  are  for  our  knowl- 
edge of  disturbances  of  metabolism. 

The  knowledge  of  02  consumption  and  COs  excretion,  conveyed  to  as  in 
the  clinical  investigations  which  are  almost  exclusively  carried  out  by  Zunt/'s 
method,  with  simultaneous  estimation  of  albumin  metabolism  (by  N"-estima- 
t i< «n  in  the  urine)  can  give  at  most  but  approximate  conclusions  regarding 
the  pari  played  by  individual  food  substances  in  combustion.  The  respiratory 
quotient  gives  as  some  information  but  the  absolute  value  of  the  transference 
of  energy  in  a  unit  of  time  cannot  be  calculated  from  the  " minute-values " 
for  Oa  and  CO...  because,  as  was  mentioned  above  t  page  8),  the  Bame  amounts 
of  carbonic  acid  and  oxygen  correspond  to  entirely  different  degrees  of  heat, 

i  Mmjnus-Lvrit,  Ztitvclir.  /'.  fcKn.  Med.,   Bd.  xwiii.  |>.  299. 


36  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

according  as  we  are  dealing  with  combustion  of  albumin,  of  fat,  or  of  carbo- 
hydrates. 

A  complete,  correct  calculation  of  force-transference  and  heat-transfer- 
ence is  only  possible  if  the  excretion  of  carbon  and  of  nitrogen  is  minutely 
investigated  for  a  considerable  period  of  time,  and  then  from  both  of  these 
the  implication  of  proteids  and  of  fat  is  estimated  in  metabolism.  From  the 
hour  or  minute  values,  fixed  conclusions  cannot  be  drawn  regarding  the  total 
calory  requirement ;  they  are  therefore  not  final.  We  may  hope,  however,  that 
prolonged  investigations  of  the  interchange  of  gases  (with  Pettenkofer's  or, 
even  better,  with  Hoppe- Seyler's  apparatus)  will  give  us  more  valuable  con- 
clusions for  pathology,  and  decidedly  broaden  our  knowledge  regarding  total 
metabolism. 

The  cases  in  which  the  entire  interchange  of  forces  in  pathologic  condi- 
tions has  been  determined  by  sufficiently  exact  technical  investigations  are  up 
to  the  present  time  very  few.    We  owe  them  mostly  to  the  labors  of  Kubner. 

In  his  researches  in  artificial  nutrition  carried  on  with  Heubner  '  in  a 
normal  and  in  an  atrophic  nursling,  intake  and  output  were  directly  estimated 
in  every  way,  and  by  calorimetric  analysis  it  was  possible  to  determine  the 
actual  figures  for  the  interchange  of  forces.  It  was  shown  that  there  is  no 
altnormal  form  of  decomposition  (force-transference)  in  the  atrophic  child. 
The  diet  necessary  for  maintenance  in  the  atrophic  child  and  in  the  healthy 
nursling  correspond  very  well  if  we  make  allowance  for  small  differences  in 
digestion  and  in  the  temperament  of  the  children  (influence  of  body  rest, 
motion  and  sleep).  If  they  are  given  an  excess  of  food,  both  utilize  about 
the  same  percentage  for  heat  production,  and  about  the  same  percentage  is  de- 
posited in  the  tissues.  The  only  peculiarity  of  the  atrophic  child  is  a  lessened 
power  of  intestinal  absorption,  and  hence  a  more  profuse  production  of  feces. 

In  a  technically  complete  investigation  of  metabolism  in  an  obese  child, 
Rubner  2  was  unable  to  determine  any  diminution  of  interchange  of  forces. 
Despite  his  pathologic  predisposition,  the  boy  required  no  less  food  than  a 
healthy  boy  of  the  same  weight  tested  by  Camerer. 

On  the  other  hand  characteristic  differences  in  the  processes  of  decompo- 
sition were  found  by  Sonden  and  Tigerstedt 3  in  their  investigations  of  metab- 
olism in  men  of  various  ages.  They  conclude  from  these  that  there  is  a  greater 
life  energy  during  youth,  in  contrast  to  the  metabolism  of  the  aged,  in  which 
a  lessened  consumption  may  be  recognized.    The  heat  production  amounted : 

In  boys  of  35.2  kilos  weight to  1,322  calories 

In  men  of  67.8  kilos  weight to  1,016        " 

In  an  aged  man  of  62.3  kilos  weight to     924        " 

i  Rubner  und  Heubner,  "  Die  natürliche  Ernährung  eines  Säuglings."  Zeitschr.  f. 
Bioh.  Bd.  xxxvi,  p.  1.  "  Die  künstl.  Ernährung  eines  normalen  und  eines  atrophischen 
Säuglings."     Zeitschr.  f.  Biol.,  Bd.  xxxviii,  p.  315. 

-  Rübner,  Beiträge  zur  "Ernährung  im  Knabenalter  mit  besonderer  Berücksichtigung 
der  Fettsucht,"  Berlin,   1002. 

s  Sonden  and  Tigerstedt, ." Untersuchungen  über  die  Respiration  und  den  Gesammt- 
stoffweehsel  des  Menschen."    Skand.  Arch.  f.  Physiol.,  1895,  Bd.  vi. 


THE  FOOD  REQUIREMENT   OF  THE  SICK  37 

In  view  of  the  criticisms  which  Camerer  and  Rubner  have  devoted  to  these 
investigations  we  shall,  however,  withhold  acceptance  from  the  conclusions 
which  Sonden  and  Tigerstedt  have  drawn  from  their  researches  in  regard  to 
the  varying  intensity  of  the  processes  of  metabolism  in  the  young  and  in  the 
aged.     (.Sec  Table.) 

THE  MAINTENANCE  DIET  AND  THE  PROTEID   REQUIREMENT 

OF  THE  SICK 

Besides  the  complete  technic  and  investigations  which  can  be  carried  on 
by  means  of  complicated  apparatus,  we  can  use  at  the  bedside  a  -impler  method 
to  determine  the  total  metabolism,  viz.:  the  calculation  of  the  tension  power, 
based  upon  the  food  which  has  been  consumed.  The  demonstration  in  Rub- 
ner's  studies  that  to  supply  suitable  energy  the  food  of  man  must  be  adapted 
to  his  condition  of  life  permits  the  conclusion  that  if  the  individual,  although 
ill,  maintains  his  body-weight,  the  supply  of  force  present  in  his  food  corre- 
sponds with  his  metabolism  (interchange  of  force). 

The  calculation  of  the  energy  value  of  food  from  the  standard  figures 
given  by  Kühner  is  simple,  and  is  in  general  use  To-day.  The  only  question 
that  arises  is  whether  the  control  of  the  body-weight  and  the  frequen!  com- 
putation of  the  NT-balance  is  sufficient  to  indicate  all  important  changes  in 
the  material  condition  of  the  body. 

But  for  the  clinical  pathology  of  metabolism  this  is  certainly  sufficient, 
and  with  the  proviso  that  this  assumption  is  justifiable,  the  quantitative  anal- 
yses of  metabolism  in  patients,  now  coming  into  common  use,  give  lis  valuable 
points  for  the  administration  of  food  suitable  for  the  maintenance  of  the 
organism  in  special  diseases,  cither  hypernutrition  ot  hyponutrition. 

A  few  of  these  investigations  have  I n  mentioned.     It  would  extend  this 

article  too  much   if  I  were  to  enumerate  them  all:  and  some  of  them  will  he 
referred  to  later.     (See  absorption  investigations.) 

v.  Xooi-dm'-  systematic  tests  of  the  energy  value  of  food  and  his  method-; 
of  producing  a  rapid  increase  in  weight,  will  be  described  explicitly. 

In  eight  women  who  were  confined  to  their  beds  weigh!  began  to  increase 
when  the  food  reached  the  following  value-:  86,  36.5,  19,  32,  33,  36,  36,  38.5, 
39  calories  per  kilogram  and  per  day.  Upon  the  average  32  calories  per  kilo- 
gram. 

In  five  women  who  were  out  of  bed  for  two  to  three  hours  during  the  «lay, 

increase  in  weigh!  began  when  the  value  of  the  f 1  reached  28,  31.5,  34, 

36.5,   10  calories  per  kilogram  and  per  day.     Dpon  the  average  •">  I  calori 

In  lour  women  who  -pent  mos!  of  the  day  out  of  bed,  and  occasionally 
walked  abou!  in  the  garden,  increase  in  weigh!  began  when  the  value  of  food 
reached  32,  37,  '■'>'•.  II  calorie-.    I'pon  the  average  31  calories  per  kilogram. 

Although  these  figures  demonstrate  thai  increase  of  weigh!  occasionally 
occurs  even  when  the  calory  \alue  of  the  food  is  very  slight  (27  calories),  aever- 
theless  v.  Noorden  caution-  us  thai  food  in  which  the  calory  value  is  less  than 
30  calories  per  kilogram  should  not  be  used.  The  increase  in  weigh!  with 
small  calory  values  is  usually  limited  to  patient-  in  whom  prolonged  under- 
nutrition has  led  to  a  decided  diminution  of  the  amounl  of  water  in  the  body. 


38  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

so  that  the  increase  in  weight  observed  may  be  referred  more  to  a  satiation 
of  the  demand  of  the  tissues  for  water  than  to  an  actual  gain  in  substance.1 

Yet  it  cannot  be  doubted,  in  view  of  these  experiments,  that,  in  emaciated 
individuals,  administration  of  food  of  very  slight  calory  value  may  compen- 
sate completely  for  the  food  requirement  and  the  interchange  of  force,  and 
may  even  permit  an  increase  in  weight.  #  For  if,  in  spite  of  a  slight  calory 
administration,  N-equilibrium  has  been  maintained  for  a  long  time  and  albu- 
min actually  accumulated,  there  cannot  be  a  calory  deficit  for  any  length 
of  time.  Later  investigations  in  metabolism  show  that  the  N-balance  is  to  a 
great  extent  independent  of  the  calory  supply.  The  stimulation  of  albumin 
accumulation  which  results  from  muscular  exertion  as  well  as  from  growth 
makes  possible  an  X-retention  even  with  an  insufficient  calory  supply  and  an 
actual  loss  in  weight  (Caspari  -). 

But  there  are  many  observations  showing  that  after  prolonged  under- 
nutrition,  such  as  occurs  in  disease,  the  body  may,  up  to  a  certain  point,  adapt 
itself  to  a  smaller  amount  of  food.  It  limits  itself  to  the  functions  absolutely 
necessary  to  maintain  life,  and  under  these  conditions  the  slightest  increase 
in  food  soon  brings  about  an  increase  in  weight  as  well  as  a  retardation  of 
the  pathological  processes,  under  the  action  of  which  the  body  has  become  so 
reduced.  The  lessening  of  body-weight,  upon  whose  maintenance,  according 
to  Pflüger,  the  energy  of  metabolism  is  dependent,  becomes  here  the  direct 
cause  of  a  diminished  rate  of  metabolism. 

The  emaciation  which  is  the  invariable  consequence  of  many  diseases  finds 
its  chief  expression  in  the  decrease  of  body-weight,  so  that  frequent  weighings 
of  the  body  in  chronic  diseases  are,  as  Gerhardt  says,  almost  as  valuable  as 
the  temperature  record  in  acute  diseases.  The  variations  may,  however,  be 
due  to  various  causes. 

"When  patients  suffering  from  gastric  disease  are  emaciated  this  is  often 
due  wholly  to  the  poverty  of  the  calory  value  of  their  food,  as  was  first  emphat- 
ically stated  and  clearly  proven  by  v.  Noorden.  The  fear  of  pain,  or  a  false 
estimation  of  the  nutritive  value  of  individual  foods,  may  have  aided  in  bring- 
ing this  about.  If  food  of  normal  calory  value  be  given,  the  loss  in  weight 
ceases. 

Other  patients  (Graves'  disease),  as  we  have  noted,  lose  weight,  in  spite 
of  a  calory  intake  sufficient  for  the  healthy,  because  the  intensity  of  the 
process  of  combustion  is  decidedly  increased.  If  the  capacity  for  taking  food 
is  great,  as  in  many  afebrile  tubercular  patients  and  in  many  cases  of  Base- 
dow's disease,  the  calory  contents  of  their  food  need  only  be  increased  beyond 
the  usual  needs  of  the  healthy,  and  they  will  not  only  attain  their  N-equi- 
librium,  but  will  very  soon  begin  to  accumulate  fat. 

This,  however,  does  not  succeed   in  all  cases.     Fr.  Müller3  was  the  first 

i  r.  Voorden,  "  Stoffverbrauch  und  Nahrungsbedarf  in  Krankheiten."  Arbeiten  aus 
dem  städt.  Krankenhaus  zu  Frankfurt  a.  M ..  1896,  p.  3. 

2  Caspari,  "  Ueber  Eiweissumsatz  und  Ansatz  bei  der  Muskelarbeit."  Pßiiger's 
Arch.,  Bd.  lxxxiii.  p.  Ö09. 

3  Fr.  Müller,  "  Stoffwechsel  bei  Krebskranken."  Zeit  sehr.  f.  klin.  Med.,  Bd.  xvi, 
p.  496. 


THE  FOOD  REQUIREMENT   OF   THE  SICK  39 

to  note  in  his  cancer  patients  that  in  malignant  cachexia,  oven  with  a  plenti- 
ful calory  supply  (with  sufficient  alhumin  elements  in  the  food),  it  was  often 
impossible  to  attain  X-equilibrium.     Gärtig  '  confirmed  these  reports. 

Here  a  toxin  damages  the  protoplasm  of  the  cells,  and  the  albuminous 
debris  of  cells,  decidedly  beyond  the  requirements  of  the  pathologic  organism 
for  albumin,  enters  the  circulation,  there  to  suffer  complete  destruction. 

In  fever  patients,  in  whom  the  extraordinarily  high  urea  figures  obtained 
by  former  investigators  (Traube  and  Naunyn)  were  for  a  long  time  empha- 
sized, we  now  have  numerous  analyses  of  metabolism  some  of  which  show 
that  the  destruction  of  tissue  in  acute  cases  of  fever  cannot  be  entirely  pre- 
sented by  any  mode  of  nutrition  (v.  Leyden  and  Klemperer2). 

The  same  is  also  true  of  certain  severe  forms  of  anemia.  Ye\  the  increased 
decomposition  of  albumin  does  not  always  occur  in  impoverished  conditions 
of  the  blood.  We  know  this  from  the  researches  of  v.  Noorden,  who  conducted 
exact  analyses  in  metabolism  in  severe  chlorosis,  which  prove  beyond  doubt 
that  such  patients,  with  the  ordinary  calory  supply  and  without  particularly 
large  amounts  of  albumin,  are  able  to  maintain  their  X-equilibrium  (Lip- 
mann- Wulff  ::).  On  the  other  hand,  there  are  certain  clinical  cases  character- 
ized by  a  severe  course,  the  so-called  pernicious  anemias,  some  of  which  are 
to-day  explained  by  the  presence  of  intestinal  parasites;  in  these  the  proteid 
metabolism  is  pathologically  increased.  Even  the  first  clinical  observers 
the  disease  (Strümpell,  Eichhorst)  found  in  these  patients  high  urea  value-. 
though  of  course  these  figures,  without  simultaneous  observation  and  analysis 
of  the  food,  did  not  prove  anything.  Exact  analyses  of  metabolism  which 
Rosenquist4  lately  carried  out  in  patient-  with  bothriocephalus-anemia  have 
determined  with  certainty  that,  at  any  rate  in  this  form  of  pernicious  anemia. 
there  is  an  increased  decomposition  of  albumin.  These  researches  constitute 
conclusive  proof  of  the  law  of  so-called  toxogenous  decomposition  of  albumin, 
for  they  illustrate  how.  shortly  after  the  expulsion  of  the  parasites  (five  to  six 
day-  later),  an  accumulation  of  albumin,  formerly  impossible,  was  attained. 
As  the  lilo.nl  changes  here  depend  upon  toxic  action,  after  the  removal  of 
which  normal  regenerative  changes  take  place,  so  also  the  pathologic  decom- 
position of  albumin  may  be  readily  -topped  by  expelling  the  parasites. 

The  indications  for  preventing  the  threatening  tissue  destruction  in  febrile 
and  cachectic  patient-  are  much  more  obscure.  Vet  this  i-  often  of  para- 
mount importance  in  dietotherapeutic  endeavors. 

Practical  experience  -how-  that  the  two  method-  which  improve  the  albu- 
min balance  in  the  healthy  are  al-o  applicable  here.  By  the  administration 
of  a  liberal  albumin  diet,  the  N"-loaa  may  be  diminished  during  fever  (Bauer 

and    Künstle)  ;   the   -aine   re8uU    can    be   obtained    by   giving   a    profuse   calory 

supply  of  NT-free  substances.     For  both  processes  excellent  methods  are  found 

•  //.  Gär  tig,  "  Untersuchungen  liber  den  Stoffwechsel  in  einem  Pall  von  Care.  (Esoph- 
agi."   Diss.,  Berlin,  L890. 

-  o.  Leyden  and  0.  Klemperer,  "Ernährungstherapie  in  acuten   Fieberkrankheiten." 
••  Handbuch  d.  Ernährungsther.,"  Bd.  ü.  p.   i|ls 

i  Lipmann-Wulff,  "  Ueber   Eiweisszersetzung  bei   Chlorose."     Die$.t   Berlin,    1891. 

*  Rosenquistf  Berl.  Um.  Wochensohr.,  1901,  p.  •  ■ 


40  ANALYSIS  OF   DISTURBANCES  OF  METABOLISM 

in  the  tables  of  v.  Leyden  and  Klemperer  {Joe.  cit.).  That  the  carbohydrates 
in  themselves  are  superior  to  the  fats  as  albumin  savers  (see  page  21)  and 
that  they  are  especially  valuable  in  the  diet  of  fever  and  cancer  patients  as 
compared  with  albumin  and  fat  (the  administration  of  which  is  frequently 
limited  by  an  unconquerable  repugnance  and  by  difficulty  in  digestion),  is 
clearly  shown  by  experience  at  the  bedside  as  well  as  by  experimental  study. 
In  fever  artificially  produced  May  1  found  a  limitation  of  the  combustion  of 
albumin  as  a  result  of  the  profuse  intake  of  carbohydrates. 

In  spite  of  the  pathologically  increased  toxogenous  decomposition  of  albu- 
min the  laws  which  normally  control  the  metabolism  of  albumin  are  still 
active  in  wasting  diseases.  This  fact  should  always  be  borne  in  mind,  and 
measures  based  upon  it  should  be  employed  in  the  dietetic  treatment  of  such 
cases.  Hirschfeld  2  succeeded  by  forced  feeding  in  attaining  an  NT-accumu- 
lation in  tuberculous  febrile  cases,  v.  NToorden,  in  his  text-book,  mentions 
quite  a  number  of  patients  with  temperatures  of  over  101.3°  F.  in  the  late 
weeks  of  typhoid  cases  running  a  slow  course,  also  patients  with  sepsis  and 
pulmonary  tuberculosis,  who  on  a  diet  rich  in  albumin  but  not  of  particularly 
high  calory  value  were  able,  at  least  for  two  weeks,  to  maintain  their  body- 
weight. 

Whether  nitrogen-equilibrium  actually  existed  in  these  cases  cannot  be 
determined  from  the  figures  given.  There  is  a  great  difference  as  regards 
the  NT-balances  in  febrile  and  those  in  non-febrile  convalescents  for,  with  the 
same  calory  supply,  we  can  produce  in  afebrile  cases  a  decided  gain  in  albu- 
min while  in  febrile  cases  we  can  scarcely  maintain  the  nitrogen-equilibrium. 

The  "  intoxication  necrosis  "  of  the  tissues  which  occurs  in  febrile  dis- 
eases as  well  as  from  under-nutrition.  and  the  deleterious  effects  of  which 
cannot  be  prevented  by  any  known  means,  is  followed  in  convalescence  by  a 
remarkable  endeavor  of  the  enfeebled  cells  to  recuperate.  They  attempt  to 
gorge  themselves  with  albumin,  and  the  balance  of  metabolism  which  termi- 
nated in  a  nitrogen  deficit  suddenly  begins  to  show  an  NT-retention  (Diinsch- 
mann,  v.  Leyden  and  Klemperer,  Joe.  cit.). 

The  great  rapidity  with  which  this  N-retention  may  occur  despite  a  nor- 
mal calory  supply  and  normal  proteid  supply  has  been  noted  in  numerous 
studies  of  metabolism.3  In  this  connection  Lüthje's  4  latest  experiments  in 
forced  feeding  have  shown  what  can  be  done  by  means  of  abundant  food  dur- 
ing convalescence.  In  his  studies  of  convalescents  from  enteric  fever,  NT-reten- 
tion of  from  10,  12  to  even  14  grams  of  NT  per  day,  corresponding  almost  to 
100  grams  of  albumin  within  twenty-four  hours,  was  repeatedly  observed. 

This  NT-addition  is  all  the  more  remarkable  because,  in  my  opinion,  we 
must  assume  that  the  retained  nitrogen  is  utilized  for  the  production  of  living 
protoplasm,  and  therefore  is  utilized  in  the  total  metabolism. 


1  M<ni,  "  Der  Stoffwechsel  im  Fieber."    Zeitsehr.  f.  Biologie,  Bd.  xxx.  p.  41. 

2  Hirschfeld,  Deutsch.  Arch.  f.  klim.  Med.,  1SS2,  Bd.  xxx.  p.  28. 

3  Albu,  "Ueber  den  Eiweisastoffwechsel  hei  chronischer  Unterernährung."    Zeitsehr. 
f.  klin.  Med.,  Bd.  xxxviii,  p.  250;  here  also  the  other  literature. 

*  Lüthje,  Beiträge  zur  "  Kenntniss  des  Eiweissstoffwechsel."     Zeitsehr.  f.  Hin.    Med., 
Bd.  xliv,  p.  22. 


THE  FOOD  REQUIREMENT  OF  THE  SICK  41 

With  such  an  amount  of  X-retention  there  is  no  possibility  that  we  arc 
producing  only  a  temporary  retention  of  X-containing  products  of  metabo- 
lism (proteid  destruction).  Further  such  an  enormous  increase  cannot  take 
wholly  the  form  of  circulating  albumin  (in  Voit's  sense).  Neither  can  we 
call  it  "reserve  albumin"  (v.  Noorden),  if  this  term  is  meant  to  imply  that 
the  albumin  accumulated  during  convalescence  is  a  different  kind  of  albu- 
min from,  and  subject  to  other  laws  of  destruction  than,  the  ordinary  albumin 
of  the  organs. 

In  the  person  experimented  upon  by  Lüthje,  whose  diet  for  twenty  days 
averaged  62.5  grams  of  N,1  after  a  reduction  to  16.7  grains  X.  N"-equüibrium 
was  attained,  not  at  once  indeed,  hut  within  three  or  four  day-:  and  even  after 
eight  days,  when  the  research  was  stopped,  but  small  losses  of  nitrogen  were 
shown.2  In  view  of  the  obvious  tendency  toward  NT-equilibrium  in  this  case 
there  is  no  reason  to  assume  that,  in  the  subsequent  period,  all  the  nitrogen 
(  [66.78  grams)  which  had  accumulated  during  twenty  days  of  the  albumin 
period  was  again  lost.  At  any  rate,  there  was  no  loss  in  weight,  although 
the  patient  after  leaving  the  clinic  and  while  living  on  a  freely  chosen  diet 
probably  did  not  consume  a  very  large  quantity  of  albumin. 

Apparently  then  the  amount  of  his  living  cell  substance  probably  remained 
large.  Consequently,  in  later  Investigations  in  the  same  person  larger  quan- 
tities of  albumin  were  required  to  bring  about  a  large  X-retention.  a  phe- 
nomenon quite  in  accord  with  the  views  of  Pflüger,  according  to  which  the 
degree  of  the  albumin  metabolism  is  dependent  upon  the  amount  of  living 
cell  substance  of  the  body. 

We  are.  therefore,  justified  in  holding  the  view  that  the  X-retention  in 
convalescents  is  not  due  to  the  retention  of  ^-containing  urinary  products 
of  metabolism,  hut  to  an  actual  accumulation  of  albumin  which  is  equivalent 
to  an  increase  of  living  protoplasm  and.  in  a  certain  Bense,  to  an  increase  in 
the  activity  of  the  body.     Moreover,  we  musl  not  always  consider  the  muscles 

of  the  body  ahme,  and   for  this  reason  the  designation,  "muscle-f 1."  had 

better  he  avoided.  Richness  in  albumin  (increase  of  the  juices  of  the  flesh) 
is  only  the  necessary  pre-requisite  for  greal  power  in  the  musculature,  and  it  is 
exercise  and  only  exercise  which  increases  power,  on  which  capacity  for  work 

is  directly  dependent. 

On   the  other  hand   a   decided    retention   of  nitrogen,  which  doe-   iinl  mean 

an  accumulation  of  albumin  (or  an  increase  of  living  protoplasm),  is  fre- 
quently met  with  in  renal  diseases.  Disturbance  of  the  nitrogen-equilibrium 
is  upual  in  these  affections. 

Ii  is  evident  without  further  elucidation  that  in  nephritis  which  is  a  con- 
sequence of  disease  of  the  excretorj  organs  urinary  substances  arc  prone  to 

remain  in  the  body,  and  we  are  therefore  not  far  wrong,  when  we  i\\)A  rela- 
tively  small    amounts   of   nitrogen    in    the   urine    (in   comparison    with    the 

i  Corresponding  to  tin-  enormous  administration  "i  390  grams  <>f  albumin  per  day. 
-  fur  which  the  further  decrease  <>i  \  administration  to  15.6  grams  \  i-  to  !"■  made 
partly  responsible. 


42  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

amount  of  nitrogen  administered  in  the  food),  in  concluding  that  the  cause  is 
deficient  excretion  of  nitrogenous  products  of  albumin  metabolism  ( Fleischer,1 
v.  Noorden  and  Kitter  2 ) . 

Because  of  this  fact,  as  well  as  because  days  with  increased  N-excretion 
often  follow  these  periods  of  decided  X-retention,  the  N/-elimination  in  nephri- 
tis is  in  a  very  "  unaccountable  and  bizarre  state  which,  according  to  v.  Noor- 
den, characterizes  the  metabolism  of  renal  patients." 

But  we  are  here  dealing  wholly  with  disturbances  of  excretion;  there  are 
no  changes  in  the  amount  of  albumin  metabolism  (no  toxogenous  albumin 
decomposition). 

In  investigations  of  the  metabolism  of  gouty  patients  we  are  often  con- 
fronted with  irregularities  in  the  excretion  of  urea,  apparently  in  consequence 
of  functional  insufficiency  of  the  organs  of  excretion,  which  is  natural  if  we 
remember  that  renal  disease  often  complicates  gout  (Vogel,3  Schmoll4). 

It  is  interesting  to  note  that  Bosemann  5  lately  found  in  a  healthy,  or  appar- 
ently healthy,  young  man  during  a  long  investigation  in  metabolism  carried 
out  for  a  different  purpose,  a  decided  N-retention  with  subsequent  increased 
excretion  of  urea.  In  this  case  there  were  no  sufficient  grounds  for  the  assump- 
tion of  any  renal  disease.  On  the  other  hand,  the  person  experimented  upon 
had  suffered  for  years  from  a  cutaneous  affection  (occasional  attacks  of  urti- 
caria), and  it  is  conceivable  that,  in  consequence  of  this,  the  excretion  of 
water  through  the  kidneys  had  in  the  course  of  years  become  diminished  in 
favor  of  that  through  the  skin;  and  that,  therefore,  the  N-elimination  by 
means  of  the  urine  had  suffered.  However,  the  excretion  of  water  in  the  urine 
during  the  period  of  N-retention  was  never  so  slight  in  this  case  that  the 
urine  could  not  have  excreted  more  nitrogen.  Bosemann,  therefore,  expressed 
the  opinion  that  a  prolonged  ingestion  of  iodin  was  responsible  for  the  dis- 
turbance of  N~-excretion  (the  person  experimented  upon  had  suffered  from 
a  cutaneous  affection  for  years,  and  up  to  within  fourteen  days  of  the  test 
had  taken  potassium  iodid),  but  at  the  present  time  proofs  are  wanting  that 
the  secretory  activity  of  the  kidneys  can  be  thus  influenced  by  the  use  of  iodin, 
even  for  a  long  time. 

1  believe  that  every  one  who  has  made  many  quantitative  researches  in 
metabolism  has  occasionally  met  with  healthy  persons  in  whom,  in  spite  of 
the  most  careful  regulation  of  the  amount  of  the  food,  it  was  impossible  to 
attain  N-equilibrium.  In  such  persons  the  daily  N"-excretion  constantly 
varies  up  and  down  when  we  are  attempting  to  get  at  the  average  figures.  Oc- 
casionally there  are  periods  of  relatively  low  excretion  lasting  several  days 

i  Fleischer,  Klinische  und  pathologisch-chemische  Beiträge  zur  "  Lehre  von  den 
Nierenkrankheiten."     Deutsches  Archiv  f.  klin.  Med.,  vol.  xxix,  p.  129. 

2  v.  Noorden  und  Ritter,  "  Untersuchungen  über  den  Stoffwechsel  Nierenkranker." 
Zeitschr.  f.  klin.  Med.,  vol.  xix,  p.   197. 

3  Vogel,  v.  Noorden's  Beiträge  zur  "Lehre  vom  Stoffwechsel,"  1894,  Heft  2,  p.  113. 

*  Schmoll,  "  Stoffwechselversuche  an  einem  Gichtkranken."  Zeitschr.  f.  klin.  Med., 
vol.  xxix,  p.  510. 

6  Rosemann,  "Ueher  die  Retention  von  Harnbestandtheilen  im  Körper."  Pflüger's 
Archiv,  vol.  lxxii,  p.  467. 


THE  FOOD  REQUIREMENT  OF  THE  SICK  43 

followed  by  similar  periods  of  increased  X-excretion.  This  phenomenon  is 
particularly  frequent  and  familiar  when  the  subject  is  on  a  regime  rich  in 
albumin  (more  than  20  grams  of  X  in  the  daily  food). 

In  contrast  with  these  irregularities  of  the  excretion  of  nitrogen  in  the 
urine  which  occasionally  occur  in  the  healthy,  and  more  frequently  in  renal 
disease  and  in  gout,  we  have  the  NT-retention  which  is  observed  in  cachectic 
patients  during  the  formation  of  transudates  and  edemas. 

Concerning  tin'-  quite  a  number  of  investigations  have  been  made,  par- 
ticularly in  patients  with  hepatic  cirrhosis.  Several  times  during  the  reac- 
cumulation  of  an  ascites  (after  paracentesis)  the  nitrogen  balance  has  been 
estimated  (Schubert,1  Marischler  and  Ozarkiewicz2).  That  the  ^-retention 
which  is  noted  in  these  cases  does  not  indicate  an  actual  albumin  accumulation 
is  clear.  The  retained  nitrogen  is  not  utilized  as  albumin  to  build  up  tissue 
but  goes  to  form  edema  or  ascites.  Authors  have  therefore  often  spoken  of 
a  " pathological "  N-retention,  and  explained  it  by  the  hypothesis  thai  while 
the  organism  normally  possesses  the  faculty  of  destroying  albumin  and  digest- 
ing it,  this  function  is  now  lost.  Must  probably,  however,  purely  mechanical 
disturbances  of  absorption  here  play  a  role  in  causing  the  retention  of  X. 
These  disturbances  depend  upon  changes  in  the  amount  of  mineral  salt>  in 
the  fluids  of  the  body,  the  osmotic  changes  being  dependent  upon  variations 
in  the  concentration  of  these  salts  which  cooperate  with  the  active  properties 
of  the  endothelia  to  govern  absorption. 

There  is  no  considerable  interest  in  the  often-discussed  question  whether 
the  albumin  in  these  re-accumulating  transudates  (ascites)  comes  from  the 
albumin  of  the  food,  or  whether  the  body  albumin  is  utilized.  The  question 
becomes  meaningless  if  we  discard  Vbit's  differentiation  of  two  varieties  of 
albumin  in  the  body  (organic  albumin  and  circulating  albumin).  This  deci- 
sion cannot  he  arrived  at  by  analysis  of  the  mineral  metabolism  in  such  cases, 
for  the  albumin  of  the  food  has  been  absorbed,  taken  up  into  the  fluids  of 
the  body,  and  thence  also  into  the  cell  protoplasm;  thence  together  with  the 
organic  albumin  it  issues  in  the  fluids  <>)'  pathological  transudates. 

DISTURBANCES   IN   THE   ABSORPTION   OF   FOOD 

In  determining  the  food  requirement  of  a  patient,  we  must  consider  (") 
changes  in  the  amount  of  oxidation  due  to  the  disease,  ( b )  consumption  of 
albumin  due  to  toxic  influences,  and  (c)  other  factors,  important  among 
which  are  the  losses  of  energy  which  the  body  suffers  by  giving  off  food  sub- 
stances which  it  should  retain. 

These  losses  are  30  manifold  and  so  various  that  it  is  impossible  to  place 
them  side  by  side  as  equivalents.  Some  of  these  losses  are  ao\  susceptible  to 
quantitative  estimation;  on   the  other  hand,   in   so   far  as  they   are  due  t,. 

1  Schubert,  "  üeber  den  V  and  CI  Umsatz  während  der  Bildung  und  Dach  <1<t  Punk 
tion  des  Ascites  bei  Lebercirrhose."     Dissert.,  Breslau,  1895. 

-  Marischler  und  Ozarkiewicz,  "Stoffwechsel  i"i  abnehmenden]  und  Eunehmendera 
Ascites."    Arch.  /'.   Veraauungskrankh.,  rol.  v,  p.  222, 


44  ANALYSIS   OF  DISTURBANCES  OF  METABOLISM 

faulty  absorption  of  food — and  this  is  to  be  especially  discussed  here — they 
can  be  well  controlled  and  have  in  fact  been  thoroughly  investigated. 

The  loss  in  material  which  the  body  suffers  from  profuse  sweating  is  rela- 
tively slight.  But  the  heat  equivalent  that  corresponds  to  the  evaporation 
of  one  liter  of  sweat  amounts  to  no  less  than  580  calories.  We  are  justified, 
therefore,  in  speaking  of  "  exhausting  sweats." 

The  food  requirement  of  the  patient  is  decidedly  increased  by  muscular 
worl\  We  know  that  even  simple  muscular  tension,  without  any  accompany- 
ing effort,  is  expressed  in  an  increase  of  the  respiratory  metabolism.  It  is  not 
essential,  therefore,  that  there  should  be  a  pathologic  tendency  to  movement 
which  constantly  keeps  the  entire  musculature  in  action,  as  in  many  insane 
patients,  or  that  severe  convulsions  should  produce  such  shock.  On  the  con- 
trary, even  the  restlessness  of  a  patient  in  lied  with  increased  respiration  and 
cardiac  action  and.  mild  tremor,  as  frequently  occurs  in  the  susceptible 
patient,  will  bring  about  an  increase  of  oxidation.  The  degree  of  such  in- 
crease in  metabolism  cannot,  however,  be  determined  quantitatively. 

The  conditions  are  still  more  difficult  if  we  attempt  to  estimate  the  loss 
of  substance  which  the  diseased  body  suffers  in  the  discharge  of  transudates, 
in  suppurating  wounds,  in  profuse  expectoration,  in  severe  albuminuria,  in 
long-continued  hemorrhage,  and  the  like.  There  can  be  no  doubt  that,  in  all 
cases  in  which  there  is  loss  of  the  body  albumin,  the  diet  must  be  arranged 
to  compensate  for  it  if  loss  of  weight  is  to  be  prevented. 

The  conditions  are  much  plainer  when,  in  consequence  of  qualitative  dis- 
turbances of  metabolism,  the  affected  organism  suffers  loss  because  the  food 
products  are  not  oxidized  to  their  normal  end  products,  and,  in  consequence, 
material  which  is  still  capable  of  oxidation  is  present  in  the  blood,  and  is 
excreted  unoxidized  or  imperfectly  oxidized  in  the  urine. 

The  sugar  which  the  diabetic  excretes  in  the  urine  is  lost  to  the  body  as  a 
source  of  power.  If  we  fail  to  take  account  of  this  we  overestimate  the  actual 
food-requirement  and  energy-interchange  of  the  diabetic.  With  a  suitable 
diet,  in  fact  with  a  diet  of  the  same  calory  values,  we  can  produce  equilibrium 
of  metabolism  in  the  diabetic  as  in  the  healthy.  Only  the  food  must  be  given 
to  him  in  such  a  form  that  he  can  utilize  it. 

By  other  products  also,  which,  in  disturbances  of  metabolism,  are  found 
in  the  urine  (acetone,  aceto-acetic  acid,  /8-oxybutyric  acid,  cyslin,  homogen- 
tisic  acid,  etc.)  energy  is  occasionally  lost  to  the  body. 

The  organism  always  loses  energy  when  there  is  insufficient  assimilation 
of  food  in  I  he  intestines.  This  occurs  in  the  healthy,  but  is  frequently 
and  decidedly  increased  in  the  sick.  Its  amount  may  be  accurately  deter- 
mined. 

In  the  healthy  estimation  of  the  calory  value  of  feces  such  as  are  dis- 
charged by  those  on  a  mixed  diet  has  led  Rubner  to  assume  a  reduction  of 
8  per  cent,  from  the  raw  calory  value  of  the  ingested  food  as  the  average 
amount  of  energy  thus  lost.  This  calculation,  however,  is  valid  only  under 
conditions  in  which  the  feces  are  made  up  chiefly  of  the  unabsorbed  residue 


THE  FOOD  REQUIREMENT  OF  THE  SICK  45 

of  intestinal  secretions,  and  do  not  contain  remnants  of  food.  These  condi- 
tions are  realized  only  when  absorption  is  normal  and  the  food  is  suitable. 

This  assumption,  however,  is  not  true  in  health  if  the  diet  contains  sub- 
stances in  a  form  difficult  of  absorption.  In  the  sick,  in  whom  the  mechan- 
ism of  digestion  as  well  as  the  mechanism  of  absorption  is  disturbed,  the 
estimation  of  the  food  lost  in  the  feces  is  absolutely  necessary,  for  we  cannot 
estimate  it  by  simple  subtraction. 

The  analysis  of  feces  is  therefore  very  important  in  all  quantitative  clin- 
ical investigations  of  metabolism.  The  results,  compared  with  an  exact  esti- 
mation of  the  food  ingested,  give  a  clear  idea  of  the  amount  of  food  assim- 
ilated in  the  intestinal  canal. 

Voit  demonstrated  in  his  laboratory  the  energy-value  of  the  food  of  healthy 
persons  by  thus  estimating  the  part  which  remained  undigested  in  the  intes- 
tine and  in  the  feces  when  the  subject  was  given  various  diets,  simple  or  mixed. 
This  forced  as  to  investigate  the  manifold  pathologic  conditions  which  com- 
plicate the  mechanism  of  digestion  and  the  processes  of  absorption  and  to 
study  the  absorption  of  and  utilization  of  food  in  these  conditions. 

The  researches  undertaken  in  this  direction  are  extremely  numerous,  and 
only  their  most  important  results  can  be  summarized  here. 

Jn  by  far  the  majority  of  these  studies  we  have  limited  ourselves  to  esti- 
mating accurately  the  nitrogen  and  the  fat  during  the  period  of  investigation. 
In  view  of  the  fact  that  the  disappearance  of  carbohydrates  during  their  pas- 
sage through  the  intestina]  canal  is  accomplished  not  only  by  absorption 
through  the  intestinal  mucous  membrane,  hut  also  by  decomposition  (fer- 
mentation), and  hence  that  the  residue  of  carbohydrates  found  in  the  feces 
<\<>r~  not  give  a  reliable  measure  of  the  actual  amount  used,  carbohydrate  esti- 
mation in  fecc-  has  been  quite  commonly  neglected  in  these  investigations. 
Only  lately  A.  Schmidt  '  has  minutely  investigated  this  question,  and  in  his 
"fermentation  test"  has  given  a  method  for  determining  accurately  those 
portions  of  the  undissolved  carbohydrates  which  are  susceptible  to  the  fluids 
of  digestion,  yet  have  escaped  absorption.  His  proposition  to  utilize  always 
the  same  trial  meal  (qualitative  and  quantitative)  for  the  quantitative  estima- 
tion of  the  absorption  of  albumin  and  fat  in  disease  deserves  the  fullest 
consideral  ion. 

The  invest igal ion  of  the  absorption  of  food  in  pathologic  conditions,  in  so 
far  as  technic  and  quantitative  estimation  are  concerned,  has  now  reached  a 
high  degree  of  perfection. 

Comparatively  iVw  of  the  numerous  researches  in  metabolism  have  given 
noteworthy  and  positive  results  concerning  tin'  assimilation  of  food. 

The  researches  of  Vv.  Müller-  in  the  metabolism  in  jaundice,  which  are 
the  earlier  quantitative  investigations  at  the  bedside,  should  he  mentioned 
first,  since  they  determine  a  very  important  decrease  in  fat  absorption  in 
of  occlusion  of  bile  from  the  intestine. 

i  t.  Schmidt,  Deutsches  Arch.  /'.  Win.  Med.,  IM.  I\i.  pp.  280  und  546;  Verh.  gr.  f. 
innere  )/.-/..  1898  und   1899. 

»Fr.  Muli,r.  ■•  I  ntersuchungen  Qber  [kterus."    Zeitschr,  f.  Min,   Med.,  Bd.  \ii.  p.  US. 


46  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

But  also  the  negative  results  of  many  investigations  which  showed  nor- 
mal or  almost  norma]  al »sorption  in  such  pathologic  states — conditions  in 
which  with  a  certain  degree  of  justice  it  might  have  been  supposed  that  more 
serious  disturbances  were  present — have  given  a  basis  of  support  for  the 
dietetic  treatment  of  such  cases,  and  have  shown  the  fallacy  of  many  diet 
lists  based  upon  erroneous  ideas. 

1  refer  to  the  excellent  monograph  of  Ad.  Schmidt  and  J.  Strassburger,1 
in  which  the  results  of  their  researches  in  this  subject  are  compiled,  and  I 
shall  limit  myself  to  mentioning  a  few  researches. 

The  mal-assimilation  of  food  which  Fr.  Müller  found  in  patients  with 
stasis  of  bile  is  limited  almost  exclusively  to  fat.  Midler  found  in  the  feces 
of  his  patients  fat  amounting  to  87.4  per  cent,  (against  22  per  cent,  in  the 
healthy).  The  loss  in  fat  often  amounted  to  50  to  70  per  cent,  of  the  fat 
administered  as  food. 

The  same  decided  decrease  of  fat  absorption  was  afterward  observed  in 
occlusion  of  the  pancreatic  juice  from  the  intestine  without  complications 
(Deucher).2  In  a  case  of  carcinoma  of  the  head  of  the  pancreas,  in  which  no 
stasis  of  bile  was  present,  only  1 7  per  cent,  of  the  fat  introduced  was  absorbed ; 
therefore,  the  simultaneous  action  of  pancreatic  juice  and  bile  is  necessary 
for  a  sufficient  absorption  of  fat  in  man. 

On  the  other  hand,  it  appears  from  the  reports  of  investigations  that 
neither  bile  nor  pancreatic  juice  is  necessary  for  the  complete  splitting  up  of 
fats  in  the  intestinal  canal.  Not  only  the  fatty  stools  of  the  jaundiced  patient 
(Fr.  Midler),  but  also  (according  to  Deucher)  the  feces  in  occlusion  of  the 
pancreatic  duct  contain  fat  which  is  chiefly  in  a  split-up  form  (up  to  80  per 
cent.)  ;  therefore,  Deucher  teaches  that  we  cannot  count  upon  the  absence  of 
free  fatty  acids  in  the  feces  as  evidence  of  disturbances  in  the  pancreatic 
function. 

Predominance  of  free  fatty  acids,  naturally,  not  at  the  cost  of  the  neutral 
fats,  but,  on  the  contrary,  at  the  expense  of  the  soaps  (Deucher),  means  pre- 
sumably a  decrease  or  absence  of  the  pancreatic  juice  secretion. 

By  others3  in  individual  cases,  a  lessened  fat  splitting  has  also  been  ob- 
served in  connection  with  occlusion  of  the  pancreatic  juice  from  the  intes- 
tine. Volhard4  has  shown  that,  although  the  decomposition  of  neutral  fats 
is  primarily  the  function  of  the  pancreas,  in  cases  of  occlusion  of  the  pan- 
creatic juice,  fat  splitting  occurs  not  only  through  the  action  of  bacteria,  but 
also  through  the  action  of  the  gastric  juice  which  also  contains  a  fat  splitting 
ferment.  There  is  need  of  further  investigations  with  due  consideration  of 
this  factor. 

i  Ad.  Schmidt  und  •/.  Strassburger,  "Die  Faces  des  Menschen."  Bonn,   1001. 

2  Deucher,  "  Stoffwechseluntersuchungen  bei  Verschluss  des  Ductus  pancreaticus." 
Correspondenzbl.  f.  Schiceizer  Aerzte,  1898,  Nr.  11. 

3  Fr.  Müller,  loc.  cit.,  Weintraud,  "Die  Bedeutung  des  quantitativen  Stoffwechsel- 
versuches  für  die  Diagnostik  innerer  Krankheiten,  insbesondere  von  Pankreaserkrank- 
ungen."     Die  Heilkunde,  1898,  Heft  2. 

4  Volhard,  "  Ueber  das  fettspalteude  Ferment  des  Magens."  Zeitschr.  f.  klin.  Med., 
1901,  Bd.  xliii,  p.  397. 


THE  FOOD  REQUIREMENT  OF  THE  SICK  47 

Except  in  the  cases  just  mentioned  a  decided  diminution  in  the  absorption 
of  fat.  e.  g.,  as  a  result  of  disturbance  of  the  gastric  chemism,  has  not  yet  been 
observed.  With  insufficient  or  increased  HCl  in  the  gastric  juice,  and  also  in 
complete  achylia  (apepsia),  the  fat  appearing  in  the  feces  does  not  amount 
to  more,  or  to  but  very  little  more,  than  the  usual  percent;!.:''. 

On  the  other  hand,  unusually  large  amounts  of  fat  are  found  in  the  dis- 
charges in  disease  of  the  intestine  (amyloid  degeneration,1  talus  mesenterica,2 
chronic  intestinal  tuberculosis  with  chronic  tubercular  peritonitis.3  fatty  diar- 
rhea [Biedert4]). 

Regarding  the  laws  of  albumin  ahsorption  in  the  sick,  y.  Noorden6  has 
demonstrated  the  surprising  fact  that  the  absence  of  HCl  in  the  gastric 
juice,  in  spite  of  its  great  importance  for  the  peptonizing  of  the  albumin  bodies 
which  is  necessary  for  their  absorption,  nowise  influences  the  assimilation 
of  the  latter.  Patients  with  disease  of  the  stomach,  with  anacidity  and  with 
hyperacidity,  showed  a  quite  normal  power  of  albumin  absorption  in  the 
intestine. 

But  later,  in  cases  of  apepsia  gastrica8  and  of  pernicious  anemia7  in 
which  not  only  HCl  but  also  the  digestive  ferments  of  the  gastric  juice  were 
absent,  slight  diminution  in  the  absorption  of  albumin  was  observed.  It 
must,  however,  lie  remembered  that  in  these  conditions  there  is  often  not 
only  independent  disease  of  the  mucous  membrane  of  the  stomach,  but  (as  the 
anatomical  Undings  in  individual  cases  have  also  shown  )  actual  atrophy  of  the 

glands  in  the  intestinal  mucous  membrane.     Hence  it   is  easily  undersl 1 

how,  in  the  absence  of  any  peptic  effect  upon  the  albumin  in  the  stomach, 
the  vicarious  intestinal  digestion  which  ordinarily  occurs  does  nut  produce 
complete  absorption. 

The  Blight  albumin  losses  in  the  feces,  which  amount  to  from  11  per  cent, 
to  15  per  cent.,  instead  of  7  per  cent,  as  in  health,  in  these  cases  and  also  in 
complete  occlusion  of  bile  from  the  intestinal  «anal,  are  in  sharp  contrasi  with 
tin'  great  losses  which  occur  in  occlusion  of  the  pancreatic  juice  (Deucher, 

Weint  raud.   loc.   cil.  )  . 

In  extensive  disease  of  the  intestinal  mucous  membrane  (as  in  an  atropine 
nursling),8  in  intestinal  amyloid  disease,"  in  extensive  intestinal  tuberculosis10 
greai  losses  of  nitrogen  have  been  observed  in  the  feces. 

i  /';-.  Müller,  loc.  cit. 

-  Ail.  Schmidt,  loc.  cit. 

3  Weintraud,  Ute.  cit. 

*  Biedert,  Jahrbuch  der  Kinderheilkunde,  Bd.  xxviii,  p.  21. 

■'•/'.  Voorden,  "Die  Ausnutzung  dor  Nahrung  bei  Magenkranken."  Zeitechr.  f.  Min. 
Med.,  Nr.  17.  p.  137. 

o  Strauss,  "Untersuchungen  über  die  Resorption  und  den  Stoffwechsel  l><i  Apepsia 
gastrica."    Zeit  sehr.  f.  klin.   I/"/..  I'd.  \li.  p.  280. 

t Erben  und  Steyskol,  "Klinisch-chemische  Studien."  '/>  it  sehr,  f.  klin.  Med.,  Bd. 
\1.  p.  lti."). —  Morozevoski,  " Stoffwechselversuche  l»i  schweren  Anämien."  Vtrchovts 
Archiv,  Bd.  clix,  II.  ft  2. 

Rubner  und  Eeubner,  "Die  künstliche  Ernährung  eines  normalen    und  eines  atro- 
phischen Säuglings."    ZeiUchr.  f.  Biologie,  Bd.  xxxviii,  p.  315. 

■  Müller,  loc.  oit. 

lu  W'cintraud,  loc.  cit. 


48  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

Conditions  of  stasis,  as  in  disease  of  the  heart,  do  not  cause  decided  loss 
in  albumin  absorption  (Grassmann1)  neither  are  diarrheas  of  mild  grade 
combined  with  a  decrease  in  the  assimilation  of  albumin  in  the  intestine  (v. 
Hösslin).2 

We  know  from  the  researches  of  v.  Mering  that  the  al »sorption  of  carbo- 
hydrates in  the  intestinal  canal  (in  the  form  of  sugar)  does  not  take  place 
so  much  by  the  chyle  tracts  as  by  means  of  the  circulation,  and  that  they 
are  introduced  through  the  roots  of  the  portal  vein  into  the  general  circula- 
tion. We  might  expect  that  circulatory  disturbances  in  consequence  of  stasis 
of  the  portal  vein  and  in  uncompensated  valvular  disease  would  seriously 
interfere  with  the  absorption  of  albumin. 

The  investigations  of  Grassmann  in  persons  with  valvular  disease  did  not 
show  any  such  influence  from  disturbance  upon  the  circulation,  and  many 
later  studies  of  assimilation  have  not  demonstrated  a  decided  decrease  in 
carbohydrate  absorption.  Even  in  Deucher's  investigations  in  patients  with 
occlusion  of  the  pancreatic  juice  from  the  intestines,  the  absorption  of  carbo- 
hydrates is  complete.  Nevertheless,  the  pancreatic  juice  contains  the  most 
active  saccharifying  ferment  known. 

The  negative  results  obtained  probably  depend  in  part  upon  the  unreli- 
ability of  the  method  previously  in  use.  It  was  therefore  a  matter  of  great 
importance  when  A.  Schmidt  with  a  uniform  diet  (test  diet),  and  by  means 
of  a  new  method  (fermentation  test),  taught  us  to  discern  the  finer  disturb- 
ances in  the  absorption  of  carbohydrates. 

In  numerous  investigations  undertaken  in  association  with  Strassburger  3 
he  succeeded  in  recognizing  a  pathological  condition  (in  which  the  clinical 
symptoms  were  not  very  pronounced,  but,  nevertheless,  were  sufficiently  char- 
acterized by  an  incomplete  digestion  of  starch)  as  a  not  uncommon  disturb- 
ance of  function  of  the  small  intestine  (in  a  broader  sense,  including  the 
pancreas  and  the  upper  large  intestine).  Only  by  a  quantitative  study  of 
metabolism  can  a  positive  diagnosis  be  made  (intestinal  fermentative  dys- 
pepsia). 

In  conclusion  we  must  refer  to  the  great  importance  of  quantitative  clin- 
ical researches  in  absorption,  in  the  healthy  and  in  the  sick,  as  helping  us  to 
decide  upon  the  merits  of  the  nutritive  preparations  with  which  chemical  in- 
dustry has  flooded  the  market  during  the  last  ten  years.  The  new  albumin 
preparations,  in  particular,  have  thus  instigated  researches  in  the  clinic,  and 
the  studies  in  metabolism  upon  which  the  employment  of  neutrose,  eucasin, 
tropon,  plasmon,  and  roborat  are  based  are  certainly  not  few.  The  degree  of 
absorption  as  shown  by  quantitative  investigations  in  metabolism,  together 
with  practical  experience  at  the  bedside,  will  always  be  the  best  measures  of 
the  actual  value  of  such  food  preparations. 

i  Grassmann,  "Die  Resorption  der  Nahrung  bei  Herzkranken."  Zeitschr.  f.  klin. 
Med.,  Bd.  xv,  p.  1S.3. 

2  v.  Hösslin,  Experimentelle  Beiträge  zur  "  Frage  der  Ernährung  fiebernder  Kranker." 
Virehow's  Archiv,  Bd.  lxxxix,  p.  95. 

'-'Schmidt  und  Strassburger,  Deutsches  Arch.  f.  lehn.  Med.,  Bd.  lxix,  p.  570. 


CONCLUDING    REMARKS  49 


CONCLUDING    REMARKS 

In  the  pursuit  of  knowledge  regarding  metabolism  in  pathological  condi- 
tions, also  in  the  nutrition  of  the  sick,  in  the  last  twenty  year-,  ir  would 
be  unjust  to  ignore  the  importance  of  the  dynamic  point  of  view  in  the  inves- 
tigation of  the  processes  of  metabolism,  which  to-day  dominates  pathology 
as  well  as  physiology. 

On  the  other  hand,  however,  we  cannot  be  too  careful — when  reiving  upon 
a  law  based  upon  the  combustion  value  of  individual  food  products — in  con- 
sidering the  quantitative  exclusively,  or  even  to  such  an  extent  as  has  been 
the  custom  of  the  average  studenl  of  metabolism  in  the  las!  few  years. 

Primarily  it  is  practical  experience  at  the  bedside  which  should  dictate 
the  diet,  and  not  theoretical  knowledge  of  food  requirement,  however  well 
founded.  The  patient  cannot  be  nourished  with  calories  alone,  and  it  would 
certainly  restrict  the  further  progress  of  our  knowledge  of  the  laws  of  nutri- 
tion if  we  should  consider  the  caloric  value  of  the  individual  foods  more,  and 
the  individual  digestibility  and  tolerance,  the  manner  of  preparation,  etc.,  of 
foods  less. 

All  honor  to  the  calory  reckoning  of  the  food — it  is  of  inestimable  value 
in  the  treatment  of  chronic  diseases — but  we  must  beware  of  carrying  it  too 
far.  In  practice  we  have  a  sufficiently  well-founded  dietetic  treatment,  espe- 
cially in  acute  disease,  without  calory  reckonings. 

But  apart  from  tins  limitation  of  its  value  in  practical  dietetics,  which  is 
not  to  be  misunderstood,  the  purely  dynamic  conception  of  processes  of  metab- 
olism has  not  always  influenced  our  scientific  understanding  and  research  in 
these  problems  in  a  fortunate  way. 

CTpon  one  of  the  first  pages  of  Boppe-Seyler's  Physiologic  Chemistry, 
these  words  art;  italicized:  "The  process  of  life  of  the  organism  i-.  in  the 
main,  a  complete  mystery/*' 

When  we  read,  however,  in  modern  clinical  researches  in  metabolism,  that 
in  the  form  of  albumin,  fat  or  carbohydrates  only  such  and  such  calories  are 
to  be  allowed   in   the  diet,  ur  are  to  he  eliminated    from    the  diet,   in  order  to 

Increase  or  to  diminish  the  proteids  or  fat  of  the  body,  or  definitely  to  influ- 
ence the  activity  of  the  organism  in  tin-  or  that  direction,  we  mighl  almosl 
believe  that  the  veil  had  long  been  lifted  from  the  mystery,  while  in  reality 
we  are  a-  far  from  a  solution  as  we  were  in  the  period  in  which  Hoppe-Seyler 
wrote  t  he  foregoing  words. 

In  the  modern  pathology  of  metabolism  the  view  i-  constantly  becoming 
more  prominent  that  the  calory  carriers  of  the  introduced  food  are  -imply 
decomposed  in  the  daily  metabolism  of  the  body  without  having  become  <'» 
integral  constituent  of  the  organism.  This  prevent-  as  from  studying  the 
greal  problem  of  life,  and  the  investigator  gets  his  inspiration  not  from  the 
hope  of  a  Bpeedy  solution  of  the  problem  but  purely  in  the  exhilaration  of 
Bteady  work  and  Bteady  progress  upon  the  path  already  trodden;  still  the  goal 

itself  must  never  he  losl   Bighl  of. 

This,  however,  is  the  case  if  tin-  view  i-  accepted  a-  final  that  the  m] 

Ö 


50  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

of  life  was  long  ago  solved  by  the  hypothesis  that  the  organism  is  a  machine 
in  which  the  food  products  undergo  combustion  somewhat  as  in  an  oven, 
thereby  becoming  a  source  for  the  production  of  heat  and  force. 

This  is  what  Liebig  assumed  for  the  N-free  foods  (carbohydrates  and 
fats),  which  he  therefore  designated  as  respiratory  materials;  because  they 
undergo  combustion  without  taking  part  in  the  structure  of  the  body  he  did 
not  consider  them  true  foods.  In  true  metabolism,  in  the  decomposition  of 
products,  in  labor  and  in  the  regeneration  of  tissue  destroyed  thereby,  they 
have  no  part  according  to  his  conception.  And  when  Yoit  explained  the 
decided  increase  of  albumin  decomposition  upon  adding  albumin  to  an  already 
sufficient  diet  by  an  increase  of  "circulating  albumin,"  and  (in  place  of  the 
"  luxury  consumption "  of  albumin,  which  was  the  current  theory)  showed 
the  special  conditions  of  decomposition  of  circulating  albumin,  making  it 
responsible  for  the  increase  in  albumin  decomposition,  then  it  was  proclaimed 
that  albumin  also  may  be  decomposed  without  being  taken  up  into  the  organic 
parts  of  the  body.  Thus  the  opinion  became  more  deeply  rooted,  favored  by 
the  purely  dynamic  conception  of  the  food  products  as  carriers  of  energy, 
that  without  any  entrance  of  the  food  into  the  tissue  of  the  living  cells,  the 
condition  of  the  body  could  be  influenced  by  the  food  in  the  circulation,  where 
the  nutritive  products  were  supposed  to  be  built  up  by  transference  into  higher 
stages  of  oxidation.  In  this  manner  the  organism  was  supposed  to  be  able  to 
utilize  its  food  and  the  energy  resulting  to  cover  its  losses  in  heat  and  mechan- 
ical labor. 

This  conception  found  decided  support  in  the  demonstration  by  Yoit  that 
muscular  labor  does  not  go  hand  in  hand  with  an  increased  albumin  decom- 
position. 

Many  objections  may  be  raised,  however,  to  such  a  conception  of  the 
processes  of  nutrition.  Since  this  conception  occurs  particularly  in  the  arti- 
cles on  metabolism  written  by  clinical  pathologists  it  is  probably  to  be  ex- 
plained by  the  historical  development  of  the  pathology  of  metabolism  on  the 
basis  of  Yoit's  law  of  metabolism  and  nutrition. 

Certainly  much  would  have  been  otherwise  if  the  principles  which  Pflüger 
advocated  in  his  numerous  publications  had  been  accepted. 

In  many  clinical  researches  of  metabolism  the  subject  of  investigation  can 
only  be  comprehended  after  considering  its  historical  development. 

I  shall  only  refer  to  the  question,  still  mooted,1  whether  alcohol  is  a 
nutrient  and  an  albumin  saver.  As  a  carrier  of  energy  alcohol  is  of  even 
greater  importance  than  the  carbohydrates,  the  recognized  albumin  savers 
(one  gram  of  alcohol  —  7  calories,  one  gram  of  carbohydrates  =  4.1  calo- 
ries). 

How  could  this  question  have  been  so  long  disputed  if  alcohol,  following 
the  dynamic  laws,  simply  undergoes  combustion  in  the  body,  and  in  this 
manner  offers  its  energy  value  to  the  organism  ?  And  why,  in  the  numerous 
clinical  investigations  of  metabolism  in  regard  to  the  albumin-saving  action 

i  J?.  Rosemann,  "Ueber  die  angebliche  eiweisssparende  Wirkung  des  Alkohols." 
Pfliiger's  Arch.,  Bd.  lxxvii,  p.  405 ;  here  also  the  other  literature. 


CONCLUDING   REMARKS  51 

of  alcohol,  does  it  so  constantly  strike  us  that  the  results  of  research  are  con- 
flicting and  permit  different  explanations? 

Because  the  whole  process  is  without  douht  quite  different  from  our  ordi- 
nary dynamic  conception  of  it.  Alcohol,  after  absorption,  is  not  only  decom- 
posed into  carbonic  acid  and  water,  and  thus  converted  into  a  definite  amount 
of  heat,  but,  moreover,  it  enters  the  protoplasm  of  the  cells  where  all  oxida- 
tion takes  place,  and  there  modifies  the  destruction  of  the  protoplasm. 

For  the  same  reason  the  carbohydrates  and  fats  do  not  act  isodynamically 
in  regard  to  albumin  saving,  as  would  he  the  case  if  the  supply  of  heat  repre- 
sented by  them  became  free  in  the  circulation.  In  fact  the  carbohydrates 
are  more  active  than  the  fats  in  the  physiologic  experiment-. 

By  the  appearance  of  acetone  bodies  after  the  complete  withdrawal  of 
carbohydrates,  pathology  indicates  that  not  only  quantitatively,  but  also  quali- 
tatively, the  destruction  of  the  cell  protoplasm  occurs  in  different  ways,  accord- 
ing to  whether  the  carbohydrate  molecule  or  the  fat  molecule  is  found  in  the 
cell  which  dominates  the  processes  "f  decomposition. 

It  has  already  been  mentioned  that  the  newer  facts  regarding  the  condi- 
tions and  the  occurrence  of  the  accumulation  of  albumin  are  very  difficult  to 
reconcile  with  Voit's  laws  of  albumin  metabolism. 

The  fact  that  gelatin,  and  as  Mann  1  has  lately  shown,  also  elastin,  even 
although  they  are  inferior  to  fat  as  calory  carriers,  are  far  superior  as  albu- 
min savers,  certifies  beyond  doubt  that  the  nitrogen-containing  food  mole- 
cule of  the  body-cell  in  which  decomposition  takes  place  brings  with  it 
something  else  than  the  calories — something  which  influences  metabolism, 
independently  of  the  calories  which  it  brings. 

Analogous  with  this  is  the  remarkable  observation  of  Loewi,2  who  fed  a 
dog  with  N-free  starch  and  cane  sugar  as  the  sole  carriers  of  nitrogen  and 
with  soluble  products  of  continuous  pancreas  digestion  until  the  complete 
disappearance  of  the  biuret  reaction.  Thus  he  managed  in  produce  nitrogen 
equilibrium.  Therefore,  tin-  «log  musl  have  formed  albumin  synthetically 
from  the  nitrogen  carriers  in  solution  (from  amido  acids,  ammonia,  purin 
bases  and  hexon  bases). 

This  proof  was  necessary  to  throw  light  upon  many  physiologic  and  patho- 
logic processes  of  metabolism.     I  -hall  mention  only  one  more: 

According  to  the  dominant  teaching,  it  was  formerly  very  difficult  to 
answers  questions  which  arose  a-  to  the  origin  of  muscular  power.  Voil  was 
the  first  to  -how  that  increased  muscular  labor  Is  not  expressed  by  a  decide,! 
increase  of  albumin  decomposition  (in  the  balance  of  metabolism),  and.  in 
opposition  to  the  views  of  Liebig  who  believed  albumin  decomposition  to  he 
inseparably  combined  with  the  activity  of  the  organs,  regarded  the  nitrogen- 
free  food  products  a-  the  source  of  energy  from  which  the  organs,  without 
Buffering  in  then-  Bubstance,  derived  energy  for  their  functions. 

Now  the  newer  investigations  of  Caspari  actually  -how  an  accumulation 

1  Wann,  "Ueber  das  Verhalten  des  Elastin«  im  Stoffwechsel  des  Menschen."  Arch. 
f.  Hygii  >'•■.  Bd.  \\\\  i.  p.  1 66. 

*  Loewi,  "Ueber  Eiweisssynthese  im  Thierkörper."     Oentralbl.  f.   Physiol.,   Bd.   w. 

p.  590. 


52  ANALYSIS  OF  DISTURBANCES  OF  METABOLISM 

of  albumin  (nitrogen  retention)  during  forced  muscular  labor.  Is  it  possi- 
ble that  the  muscular  machine  acts  so  wonderfully  that  it  is  not  subject  to 
wear  and  tear,  but  actually  develops  during  this  condition,  while  it  transfers 
the  energy  supplied  by  the  carbohydrates  into  living  force?  Or  are  the  con- 
ditions in  reality  quite  different,  and  are  nitrogen-free  substances  really 
burned  in  the  muscle  during  its  work,  or,  on  the  contrary,  does  it  decompose 
the  specific  albuminous  protoplasm  of  the  muscle  cell  so  that  the  nitrogen 
also  at  once  decomposes  like  the  albumin  of  the  muscle,  and  is  utilized  for 
the  reconstruction  of  muscular  albumin  ?  Verworn  assumes  that  in  muscular 
activity  the  biogen  molecule  which  represents  living  albumin  decomposes  into 
atom  groups  containing  nitrogen  and  non-nitrogenous  atoms,  of  which  only 
the  latter  are  excreted  in  metabolism,  whereas  the  former  regenerate  to  com- 
plete biogens.  That  we  must  recognize  synthetic  processes  if  we  are  to  make 
such  an  assumption,  cannot  be  thought  remarkable  after  what  has  been  said. 
For  does  not  the  animal  organism  evolve  from  inorganic  iron  such  a  highly 
complicated  molecule  as  is  represented  by  hemoglobin?  It  produces  syn- 
thetically nuclear  albumin  from  its  components,  etc. 

If  we  dismiss  the  view  that  each  molecule  of  food  which  is  absorbed,  and 
is  required  by  the  organism  to  maintain  its  vital  functions,  is  at  once  in  all 
its  constituents  decomposed  into  end-products  of  metabolism  and  quantita- 
tively excreted,  then  many  other  points  in  the  pathology  of  metabolism  for- 
merly difficult  to  understand  will  be  made  clear. 

When  nuclein  decomposition  occurs  in  the  body,  the  phosphoric  acid  ex- 
cretion is  frequently  not  uniform  with  the  excretion  of  alloxur  bodies ;  appar- 
ently because  phosphorus  is  retained  for  the  purpose  of  nuclein  synthesis,  for 
the  regeneration  of  the  nuclein  which  has  been  lost. 

After  complete  withdrawal  of  carbohydrates,  the  amount  of  sugar  excreted 
in  severe  cases  of  diabetes  (as  has  lately  been  frequently  observed)  may 
exceed  the  quantity  which  may  be  assumed  to  be  formed  from  albumin.  Be- 
fore we  speak  of  a  sugar  formation  from  fat,  we  should  think  of  a  renegera- 
tion  of  the  N-containing  part  of  the  albumin  molecule  after  splitting  off  the 
carbohydrate  group,  perhaps  with  the  aid  of  the  atom  groups  taken  from 
the  fat  molecule.  This  is,  however,  quite  different  from  a  direct  sugar  forma- 
tion from  fat  expressed  in  chemical  equation.  It  is  simultaneous  splitting 
and  synthesis,  a  work  of  the  living  cell,  whose  effort  toward  regeneration 
becomes  greater  the  more  its  protoplasm  is  involved  in  decomposition. 

In  the  study  of  the  pathology  of  metabolism,  we  must  escape  from  the 
narrow  confines  of  views  which,  in  the  discipline  of  student  days,  were  of 
certain  value  to  us,  but  which  must  no  longer  be  a  barrier  to  development. 

The  opinion  must  probably  be  discarded  that  the  amount  of  decomposi- 
tion of  animal  protoplasm  (living  substance),  that  is,  the  amount  of  metabo- 
lism necessary  to  maintain  life,  is  equal  in  all  individuals  and  at  all  times. 

Of  course  the  common  estimation  of  the  amount  of  total  energy  consump- 
tion in  clinical  metabolism  investigations  is  not  decisive  in  judging  this 
question.  Slight,  and  even  scarcely  noticeable  differences  in  the  activity  of 
different  individuals  (greater  muscular  exertion,  etc.)  may  produce  vary- 
ing degrees.     Hence  the  difference  of  two  values  obtained  under  similar  con- 


CONCLUDING  REMARKS  53 

ditions  of  research  should  not  have  too  great  importance  attached  to  it.  as  the 
identity  of  the  conditions  is  only  apparent. 

Nevertheless  the  low  nutritive  values  which  are  sufficient  to  maintain  life 
after  prolonged  wider-nutrition  and  in  some  cases  of  diabetes  are  of  no 
importance.  That  in  some  obese  persons  an  extreme  diminution  of  the 
calory  supply  is  actually  necessary  before  they  begin  to  Lose  weight  also  makes 
it  likely  that  here  a  fundamental  property  of  the  living  cells  is  changed,  so 
that  the  degree  of  their  energy  of  decomposition  has  been  diminished.  And 
the  contrary  experience  that,  in  some  perfectly  healthy  persons,  even  with 
a  food  very  rich  in  calories,  it  is  impossible  to  produce  an  increase  in  weight, 
makes  us  doubt  whether  in  this  ease  the  amount  of  food  is  really  the  decisive 
factor  in  the  interchange  of  energy.  On  the  contrary,  cases  of  this  kind 
make  it  more  likely  that  there  is  an  increased  energy  of  the  cells  and  so  an 
actual  "luxury  consumption/' 

In  practice  these  individuals  do  not  always  present  such  conspicuous  exter- 
nal -inns  of  a  lively  temperament  that  the  increase  in  metabolism  can  be  ex- 
plained by  an  increased  activity  of  the  muscles;  and  we  are  the  more  inclined 
to  search  for  an  individual  anomaly  of  protoplasmatic  activity,  if  such  an 
assumption  can  be  in  consonance  with  the  dominant  teaching. 

The  dynamic  theory,  which  has  been  of  inestimable  value  in  making  us 
recognize  in  biology  the  force  of  the  law  of  conservation  of  energy,  naturally 
lays  particular  stress  only  upon  the  intake  and  output  of  the  organism.  But 
this  theory  doe-  not  exclude  intermediary  metabolism  from  consideration  in 
the  future.  The  importance  of  inorganic  -alts  will  then  appear  in  it-  proper 
light;  they  are  indispensable  in  the  food:  nevertheless,  because  they  do  nol 
bring  tension  power  (calories)  into  the  organism  they  have  no  part  assigned 
to  them  in  the  dynamic  conception  of  the  processes  of  metabolism  and 
nutrition. 

Again  we  mn-i  remember  thai  in  the  animal  organism  we  have  not  only  ten- 
sion energy  consumed,  but  sources  of  energy  newly  formed  (ferments). 

Although  researches  in  the  realm  of  the  pathology  of  metabolism  will  be- 
come much  more  complicated,  when  all  these  facts  are  borne  in  mind  the 
desirable  resull  will  be  attained  that  clinical  pathology  of  metabolism  will 
become  deeper  but  less  expansive. 


OVER-NUTRITION    AND    UNDER-NUTRITION 

By  C.  v.    NOORDEN,   Frankfort-on-Main 

In  modern  therapy,  dietetic  cures  are  becoming  more  important  from 
year  to  year,  particularly  those  which  are  intended  to  influence  the  entire 
nutritive  condition.  Originally  confined  to  the  domain  of  internal  diseases, 
they  have  become,  familiar  to  the  surgeon  and  gynecologist,  and  no  less  valu- 
able to  them  than  to  the  specialist  in  clinical  medicine.  It  is  well  worth 
while  to  consider  the  salient  features  of  these  cures,  without  expecting  that 
much  that  is  new  will  be  promulgated.  For  the  fundamental  laws  are  well 
known,  though  their  application  to  practice  is  eternally  new.  When  the  indi- 
viduality of  each  patient  has  to  be  considered,  the  rules  lose  their  supposed 
uniformity  and  their  diagrammatic  aspect.  Uniform  and  self-evident  as  the 
method  is  when  formulated  in  theory,  in  practice  each  particular  dietetic 
treatment  brings  with  it  new  difficulties,  new  demands,  and  when  the  art  of 
the  physician  has  succeeded,  he  invariably  experiences  the  gratification  of  an 
artistic  triumph. 

1.    CONCEPTION   OF   THE    "CONDITION  OF  NUTRITION" 

When  we  speak  of  a  person's  "  condition  of  nutrition  "  we  mean,  in  the 
first  place,  his  development  of  adipose  tissue;  but  not  only  this  is  to  be  con- 
sidered, for  the  state  of  the  muscles  is  of  no  less  importance.  Their  devel- 
opment is  not  always  proportionate  to  the  amount  of  fat.  There  are  many 
persons  who  are  deficient  in  fat  and  weak  in  muscle,  and  many  who  are  rich 
in  fat  and  strong  in  muscle.  But  there  is  a  third  class  who  are  of  strong 
muscular  power  and  deficient  in  fat,  and  a  fourth  who  are  lacking  in  muscle 
and  rich  in  fat. 

Of  most  importance,  of  course,  is  the  condition  of  the  muscles,  all  the 
more  so  since  with  powerful  muscles  we  expect  a  normal  composition  of  the 
blood  and  of  the  most  important  glandular  organs.  In  every  treatment  by 
which  we  hope  to  influence  the  "  condition  of  nutrition  "  the  protection  of  the 
muscles  must  be  kept  in  mind,  or,  stated  more  generally — the  living  and  func- 
tioning protoplasm  of  the  body  must  be  protected,  and  if  possible  improved, 
so  that  the  maximum  of  its  development  may  be  attained. 

How  great  is  the  amount  of  fat  on  the  body — leaving  out  of  considera- 
tion pathologic  leanness,  pathologic  obesity  and  special  instances  (see  below) 
— is  of  less  significance.  There  is  no  generally  accepted  standard  for  a  nor- 
mal amount  of  fat.  Between  emaciation  on  the  one  hand  and  obesity  on  the 
54 


INCREASE  OF  FLESH  AND  INCREASE  OF  FAT  55 

other  hand,  there  is  a  wide  space  for  the  conception  of  a  "  medium  state  of 
nutrition."  Although  this  conception  permits  no  positive  statement  as  to 
the  amount  of  superfluous  fat,  no  definite  body-weight,  no  distinct  relation 
between  weight  and  size,  age  and  sex,  that  can  he  called  normal,  it  must, 
nevertheless,  be  maintained  [hat,  for  cadi  individual,  il/rre  is  a  definite  stand- 
ard for  the  condition  of  nutrition,  particularly  with  regard  to  the  amount  of 
fut.  To  recognize  this  optimum  is  the  duty  of  the  physician,  and  presup- 
poses much  thought  and  experience.  Good  judgment  will  take  into  considera- 
tion the  state  of  health,  the  competency  of  all  the  organs,  and  the  entire  mode 
of  life.  A  few  examples  will  illustrate  this.  Experience  teaches  us  that 
persons  who  are  predisposed  to  tuberculosis  are  endangered  by  leanness,  and 
that  a  certain  degree  of  corpulence  protects  them.  Xeurasthenics,  as  a  rule, 
feel  hotter  if  they  have  a  large  amount  of  adipose  tissue.  For  patients  suffer- 
ing from  disease  of  the  heart,  Bright's  disease,  and  emphysema  the  slightest 
amount  of  superfluous  fat  is  an  evil,  and  in  diseases  that  affect  the  organs 
of  motion,  obesity  is,  at  least,  the  cause  of  great  annoyance.  Persons  who 
perform  hard  labor  continue  in  better  health  and  are  more  capable  of  working 
if  their  adipose  tissue  is  not  too  greatly  developed.  Those  who  have  passed 
the  prime  of  life,  and  are  no  longer  compelled  to  work  hard,  bear  a  certain 
development  of  corpulency  better  than  those  just  beginning  the  struggle  for 
existence.  These  points  will  be  amplified  in  the  description  of  the  indica- 
tion- for  over-nutrition  and  under-nutrition. 

It  follows  from  what  has  been  said  that  in  all  treatment  by  which  we 
attempt  to  influence  nutrition,  we  imi-l  first  of  all  try  to  maintain  and 
improve  the  muscles;  in  certain  cases,  however,  we  attempt  nutritive  cures 
in  which  increase  or  diminution  of  adipose  tissue  represents  the  sole  aim  of 
the  treatment.  Even  in  these,  however,  the  state  of  the  muscles  must  not  be 
lost  sight  of.  The  importance  of  this  must  be  emphasized,  for  very  frequently 
it  is  forgotten.  We  sometime-  see  pal  nuts  with  weak  muscles  who  in  the 
process  of  " strengthening "  are   fattened   by  various   mean-,  ami   when   the 

CUre  is  done  we  lilld  obese  subjects  with  feeble  muscles.  Again  we  sei1  corpu- 
lent persons  subjected  to  such  irrational  antifal  cures  that  not  only  the  fat 
but  al.-o  the  muscles  and  blood  are  depleted,  and  the  activity  <d'  their  func- 
tions permanently  injured. 

Our  theme  will  be  the  question:  How  far  can  and  should  the  general 
condition  of  nutrition,  i.  c.  of  muscle  mnt  fat,  be  influenced  by  dietetic  treat- 
ment ? 

2.  INCREASE  OF  FLESH  AND  INCREASE  OF  FAT 

To    accomplish    the    most    important    point,    the    accumulation    of    mu-cle, 

dietetic  treatment  has.  unfortunately,  but   limited  powers.     Theoretically  it 

appears  to  be  mo-t  difficuH  to  maintain  the  musculature  of  the  body  in  anti- 
fat  cures.  The  animal  experiment-  of  physiologists  have  invariably  ahown 
that  with  onder-nourishmenl  fat  disappears  from  the  body,  but  that  albumin 

also  decreases.  To  this  |o--  of  hod v  albumin,  that  i-  to  -av.  wa-te  of  mu-cle. 
We   OWe    the    -erioii-    consequences    which    frequently    surprise    tho-e    who    carry 

out   a  too    rapid   antifal   cure.     Discussions   regarding  the  admixture   and 


56  OVER-NUTRITION  AND  UNDER-NUTRITION 

amount  of  nourishment  which  will  most  surely  produce  a  loss  of  fat  without 
impairing  the  muscular  condition  have  been  carried  on  for  years,  and  reached 
their  acme  in  the  debates  at  the  Congress  of  Internal  Medicine  in  the  year 
1885,  and  in  the  literary  war  waged  between  Ebstein  and  Oertel.  The  views 
were  based  rather  upon  theory  than  upon  practical  experience.  Investigations 
regarding  metabolism  during  antifat  cures  had  not  yet  been  attempted.  A 
few  years  later  when,  independently  of  one  another,  F.  Ilirschfeld  and  v. 
Noorden-Dapper  worked  out  this  problem  experimentally,  contradictions  at 
first  resulted.  The  former  found  it  almost  impossible  to  produce  a  loss  of 
fatty  tissue  without  a  simultaneous  decrease  of  the  body  albumin.  The  other 
two  authors  proved  by  numerous  investigations  that  this  goal  may  be  reached, 
and  oven  without  special  difficulty,  provided  the  leap  from  a  plentiful  diet  to 
one  of  abstinence  is  not  too  sudden.  All  the  authors  who  later  devoted  them- 
selves to  similar  researches  have  confirmed  this.  The  satisfactory  result  of 
these  studies  of  metabolism  has  had,  it  appears  to  me,  great  influence  upon 
the  practical  work  of  physicians,  and  has  encouraged  them — certainly  not  to 
the  detriment  of  the  patient — to  attempt  careful  antifat  cures,  where  pre- 
viously they  refrained  from  them  because  in  every  antifat  cure — even  if  only 
transiently — the  supply  of  body  albumin  was  jeopardized.  According  to  other 
investigations  in  metabolism  as  well  as  in  my  own,  and  also  according  to  later 
researches  of  Dapper  and  myself,  careful  planning  of  the  ingestion  of  nour- 
ishment so  that  the  albumin  supply  of  the  body  will  not  be  decreased  may 
obviate  this  danger,  but  by  no  means  removes  all  other  difficulties.  For,  in 
numerous  cases,  it  is  evident  that  the  muscular  power  of  the  patient  must  not 
only  be  maintained  but  increased.  This  end  also  may  be  practically  achieved, 
and  will  crown  the  success  of  a  thoughtfully  carried  out  antifat  cure.  It  pre- 
supposes that  the  patient  must  become  accustomed,  from  the  beginning  of 
the  treatment,  to  an  increasing  amount  of  bodily  exercise.  We  must  utilize 
the  well-known  physiological  fact  that,  if  we  exercise  a  muscle,  it  gains  not 
only  in  strengt]]  but  also  in  bulk.  It  is  true  that  investigations  of  metabo- 
lism in  which  the  combustion  of  albumin  has  been  tested  during  dietetic 
antifat  cures  with  and  without  systematic,  muscular  exercise  have  not  yet 
been  carried  out;  but  we  hardly  require  them,  for  clinical  experience  demon- 
strates how  readily  strength  and  size  of  muscles  may  be  increased  during 
dietetic  antifat  cures. 

Formerly  (in  opposition  to  the  facts)  we  regarded  the  preservation  of 
the  stability  of  the  organic  albumin  in  antifat  cures  as  difficult,  even  impos- 
sible. Yet,  at  the  same  time,  it  was  not  doubted  that  by  forced  feeding  it 
was  very  easy  to  accelerate  not  only  the  formation  of  adipose  tissue  but  also 
of  the  animate  protoplasm  of  the  body,  and  particularly  to  strengthen  the 
muscles.  The  proposition,  however,  is  by  no  means  so  simple  as  it  appears. 
That  albumin  metabolism  is  diminished  and  N-containing  material  accumu- 
lates in  the  body  on  over-feeding  with  albuminates,  particularly  with  fat,  and 
to  a  still  greater  degree  with  carbohydrates,  had  been  long  known  from  animal 
experiments  by  Bischoff  and  C.  v.  Voit  and  their  pupils.  Investigations  in 
man — especially  the  researches  of  Bleibtreu  and  Krug — have  confirmed  this, 
and  Bornstein  and  Lüthje  in  their  latest  studies  in  metabolism  have  demon- 


INCREASE  OF  FLESH  AND  INCREASE  OF  FAT         57 

strated  the  surprising  fact  that  the  amounts  of  nitrogen  which  remain  in  the 
body  in  over-nutrition  may  be  raised  in  an  astonishing  degree.  There  can  be 
no  doubt,  therefore,  that  an  increase  in  the  body  nitrogen  may  be  secured  by 
the  quality  and  quantity  of  food.  In  all  probability  we  may  go  further  and 
say  that  this  increase  of  nitrogen  means  increase  of  albumin,  i.  e.,  the  X  which 
remains  accumulates  in  the  body  in  the  form  of  albumin.  Here  our  knowl- 
edge for  the  present  ceases.  C.  v.  Voit  has  called  attention  to  the  fact  that, 
in  an  adult  animal,  the  albumin  accumulated  by  excessive  nutrition  is  stored 
up  in  a  form  readily  decomposed  and  must  therefore  be  differentiated  from 
true  organic  albumin.  Hence  he  proposed  the  name  "circulating  albumin." 
Since  it  is,  however,  extremely  unlikely  that  this  albumin  actually  "  circu- 
late." i.  e..  that  it  is  present  in  the  circulating  fluids,  and  as  it  is  very  much 
more  probable  that  it  is  deposited  in  the  cells,  I  have  suggested  the  term 
'•  reserve  albumin."  This  term  has  now  been  generally  accepted.  It  is  meant 
to  imply  that  the  albumin,  like  the  fat  globules  and  glycogen  granules,  is 
absorbed  into  the  body  of  the  icll.  and  is  deposited  there  for  a  time  (as  reserve 
material)  without  becoming  an  integral  constituent  of  the  cell  protoplasm. 
According  to  this,  in  the  investigations  conducted  with  me  by  Krug,  and  in 
my  Text-Book  of  the  Pathology  of  Metabolism,  I  have  regarded  it  as  unproven 
and  improbable  that  the  increase  of  body-albumin  which  may  readily  lie 
attained  is  synonymous  with  increase  of  muscle.  Increase  of  muscle  should 
mean  the  increase  of  living  cell-albumin.  But  the  mass  of  blood-cells  and 
gland-cells  unquestionably  is  hut  little  influenced,  and  this  is  especially  true 
of  muscle.  With  few  exceptions  (prominenl  among  them  E.  Pflüger  and 
Bornstein)  later  authors  have  accepted  this  view,  and  in  a  recent  excellent 
and  instructive,  as  well  as  critical,  dissertation  by  Lüthje,  who  has  produced 
by  far  the  greatesl  increase  of  body-albumin,  we  find  the  same  opinions  ex- 
pressed. If  increase  of  albumin  (so  readily  attained)  were  synonymous  with 
increase  of  true  muscle  tissue  weaklings  could  without  great  difficulty  ho 
transformed  into  robust,  muscular  people.  But  this  is  of  course  impossible. 
Every  one  knows  that  over-nutrition  will  produce  corpulent  persons,  but  not 
athlete-. 

Increase  of  muscle  is  a  function  of  the  specific  growth  energy  of  the  cells, 
i.  i ..  of  cellular  activity  rather  limn  of  excessive  nourishment.  Hence  we  see 
plentiful  and  permanent  increase  of  muscle: 

1.  In  every  growing  body. 

2.  In  the  fully  grown  body  when  it  is  gradually  accustoming  it-elf  to 
increased  labor  (work  hypertrophy  of  the  muscles). 

'■'<  When,  from  previously  insufficient  Qourishmenl  or  from  disease,  the 
muscular  tissue  of  the  body  has  been  diminished,  and  subsequently  profuse 
Qourishmenl  makes  up  this  loss.  It  is  a  fundamental  error  to  look  for  the 
primary  cause  of  this  variety  <>f  muscle  accumulation  in  food  ;  it  i-  an  expres- 
sion of  the  regenerative  energy  of  the  cells.  This  is  a  mighty  power.  It  Bhows 
itself,  a-  investigations  in  the  metabolism  of  convalescence  have  demonstrated, 
even  when  there  is  do  question  of  forced  feeding,  and  indeed  when  the  calory 
supply  is  so  slight  that  fat  must  certainly  be  loal  in  the  body,  and  even  a 
healthy  person  would  lose  body  albumin. 


58  OVER-NUTRITION  AND  UNDER-NUTRITION 

Of  course,  under  circumstances  otherwise  favorable  for  the  accumulation 
of  albumin,  inuscular  development  takes  place  more  certainly  and  more  rap- 
idly with  very  profuse  nourishment  than  with  scant  food.  Usually,  however, 
in  adults  otherwise  healthy — provided  we  consider  long  periods  of  time  and 
not  brief  intervals — muscle-increase  is  independent  of  an  excess  of  food. 
Muscle  growth  is  dependent  on  food  supply  only  because  the  body  is  better 
supplied  by  over-nutrition  with  reserve  products  (glycogen,  fat,  reserve  albu- 
min), and  because  better  food  and  the  somatic  and  psychical  stimulation 
resulting  from  it  produce  greater  capacity  for  work.  To  this  greater  capacity 
of  the  muscles  and  secreting  glands  for  work  and  the  stimulus  for  blood  for- 
mation which  arises  thereby,  the  body  owes  its  power  of  accumulating  proto- 
plasm as  well  as  fat,  and — what  is  more  important — of  permanently  retain- 
ing it. 

From  this  point  of  view,  it  appears  that  under  special  conditions  (after 
wasting  disease  or  after  prolonged  periods  of  hunger  and  under-nutrition)  we 
may  hope  by  over-alimentation  to  promote  the  formation  of  new  protoplasm, 
and  particularly  of  muscular  substance.  The  natural  regenerative  endeavor 
of  the  organism  will  aid  us.  If,  however,  we  are  treating  persons  who, 
although  weak,  are  sufficiently  well  nourished,  the  chances  for  increased  mus- 
cular development  are  much  more  uncertain. 

In  such  debilitated  individuals,  especially  in  convalescents,  the  accumula- 
tion of  flesh  will  be  greatly  favored,  if  from  the  onset,  or  as  soon  as  the 
strength  at  all  permits  it,  forced  feeding  is  combined  with  muscular  exercise. 
This,  however,  contradicts  a  widely  prevalent  custom;  for,  in  the  original 
methods  of  Playfair-Mitchell,  most  patients  who  were  to  undergo  forced 
feeding  were  advised  either  to  go  to  bed  or  to  keep  as  quiet  as  possible.  In 
certain  cases,  for  example,  in  very  irritable  nervous  persons,  this  may  be  fully 
justified.  Generally,  however,  it  appears  to  me  after  years  of  experience  that 
early  and  sufficient  activity  of  the  muscles  is  much  more  beneficial  when  we 
desire  to  nourish  our  patient.  The  increase  in  weight  is  not  less  than  in  rest 
cures,  and  it  is  gratifying  to  note  that  the  patients  gain  in  muscular  strength 
and  activity  at  the  same  time  that  they  increase  in  weight  and  size.  There 
is  very  little  danger  that,  in  consequence  of  muscular  exercise,  much  of  the 
fat  which  has  been  acquired  with  difficulty  may  lie  again  lost,  since  the  in- 
crease of  appetite  induced  by  muscular  exercise  easily  makes  good  the  material 
used  up. 

In  view  of  what  has  been  said  it  is  obvious  that  in  forced  feeding,  as  well 
as  in  carefully  and  wisely  conducted  antifat  cures  (for  obesity),  the  increase 
and  strengthening  of  the  muscles  is  almost  independent  of  the  loss  or  accumu- 
lation of  fat.  Insufficient  nourishment  in  obesity  favors  the  loss  of  muscle; 
superfluous  nourishment  both  in  normal  nutrition  and  when  it  is  below  par 
favors  the  accumulation  of  muscle.  But  muscle-loss  and  muscle-increase  are 
not  in  immediate  dependence  upon,  or  in  exact  proportion  to,  the  quantity  of 
food.  An  individual  factor  always  intervenes;  an  elective  property  of  the 
organism  rather  than  the  bulk  of  food  produces  muscle-accumulation. 

The  conditions  are  quite  different  in  losses  and  accumulations  of  fat. 
Here  the  law  may  be  definitely  stated.     When  the  supply  of  nourishment  is 


OCCURRENCE  AND  CONSEQUENCES  OF  UNDER-NUTRITK  »N  59 

less  than  the  requirement  for  maintenance,  fat  is  always  lost;  when  it  is 
greater  than  the  requirement  for  maintenance  fat  is  always  accumulated.  In 
the  former  case  we  speak  of  under-nutrition,  in  the  latter  case  of  over- 
nutrition. 

Although  I  shall  he  repeating  what  is  known  to  most  readers,  it  is  neces- 
sary to  devote  a  few  lines  to  the  definitions  of  food  necessary  for  maintt  nance, 
of  over-nutrition,  and  of  under-nutrition. 

In  proportion  to  the  requiremenl  of  the  colls,  according  to  the  amount  of 
work  required  of  them  externally  and  internally  in  heat  production,  etc.,  the 
body  arranges  the  use  of  material  for  combustion.  When  the  combustion 
value  of  the  food  is  equal  to  the  demand,  the  equilibrium  of  metabolism  in 
tin'  body  is  preserved.  The  amount  of  food  which  is  necessary  for  this  we 
call  "food  necessary  for  maintenance"  Most  normal  persons,  if  Lefi  to  them- 
selves and  following  their  own  inclination-,  usually  take  neither  more  nor 
Less  food  than  is  necessary  for  maintenance;  variations  in  this  balance  of 
nutrition  may  occur,  but  the  deficiency  of  one  day  is  made  up  the  next.  Con- 
sequently it  is  the  rule  that  normal  adult-  remain  for  years  and  decades  at 
about  the  same  weight.  The  proportion  of  food  which  is  necessary  for  the 
equilibrium  of  metabolism,  calculated  per  day  and  for  each  kilo  of  the  body- 
weight,  must  have  a  combustion  value  of  from  thirty  to  thirty-five  calories  in 
complete  rest  (in  bed),  thirty-five  to  forty  calories  with  lighl  exercise,  forty 
to  forty-five  calories  with  moderate  exercise,  and  forty-five  to  sixty  calories  in 
exhausting  muscular  labor. 

For  children  these  figure-  are  to  be  raised  about  one-third,  for  the 
they  are  to  be  lowered  about  one-fourth.  There  are  no  decided  differences 
between  males  and  femali  -.  T  •  -••  figures  relate  to  a  "  moderate  condition 
of  nutrition"';  in  the  obese  they  are  from  twenty  to  twenty-five  per  cent. 
lower,  in  very  thin  persons  they  are  just  as  much  higher,  for  while  fat  in- 
creases the  body-weight  it  take-  qo  pari  in  metabolism.  This  ratio  will  enable 
u-  to  calculate  the  amount  of  food  necessary  in  the  individual  case  with  suffi- 
cient exactness  for  practical  purposes. 

3.    OCCURRENCE    AND    CONSEQUENCES   OF    UNDER-NUTRITION 

A-  -oon  as  the  supply  of  food  ( i.  e.,  it-  combustion  value)  falls  below  that 
required  for  maintenance  we  have  a  Btate  of  hyponutrition.  The  onder-nour- 
ished  body  doc-  not  accommodate  it-  combustion  processes  to  a  lower  Bcale — - 
except  perhaps  in  the  mosl  extreme  marasmus  and  in  the  death  agony.  When 
the  supply  is  Less  than  the  requirement,  it  lives  upon  its  own  body  substance. 
In  the  obese,  a-  we  have  -ecu.  this  process  may  be  limited  to  the  adi] 
tissue  while  the  albumin,  thai  is,  the  muscle,  is  preserved.  In  normal  and 
mal-nutrition,  however,  apart  from  exceptional  cases  (in  convalescence  after 
acute  diseases,  or  after  periods  of  hunger),  the  supply  of  albumin  in  the  body 
may  also  be  slowly  consumed,  and  the  person  nol  only  loses  fal  bul  becomes 
weaker  in  muscle.  We  rarely  resorl  to  systematic  under-nutrition  except  in 
the  treatment  of  obesity.  Whether  or  nol  treatment  for  obesity  is  indicated 
doc-  not  depend  wholly  upon  the  degree  of  corpulence,  but  also  npon  many 


60  OVER-NUTRITION  AND  UNDER-NUTRITION 

other  conditions,  particularly  upon  the  healthy  state  of  certain  organs,  for  ex- 
ample the  heart  and  the  kidneys.  To  this  we  shall  refer  later.  But  very  often, 
without  our  interference  and  against  our  will,  our  food  produces  the  character- 
istics of  hyponutrition.  This  occurs  in  many  diseases.  We  are  unable  to  main- 
tain the  balance  of  nutrition  either  because  patients  refuse  to  take  a  sufficient 
supply,  or  because  diseases  of  certain  organs  (for  example,  the  stomach) 
necessitate  a  limitation.  In  acute  diseases  which  run  a  rapid  course  the  dan- 
ger is  not  great,  for  what  has  been  lost  is  rapidly  regained  in  convalescence. 
But  in  chronic  diseases  the  body  is  often  more  weakened  and  damaged  by  con- 
tinued under-nutrition  than  by  the  disease  itself.  It  then  becomes  one  of 
the  most  important  duties  of  the  physician  to  increase  the  amount  of  food 
at  least  to  the  point  of  maintenance,  and,  if  possible,  to  make  up  what  has 
been  lost  by  forced  feeding.  He  will  then  often  have  the  pleasure  of  noting 
that  not  only  does  the  state  of  nutrition  improve,  but  that  this  improvement 
acts  favorably  in  the  cure  of  the  disease.  In  some  maladies,  for  instance,  in 
not  too  far  advanced  tuberculosis  of  the  lungs,  this  is  the  rule. 

At  least  as  frequently  as  in  actual  disease  we  meet  persons  who  are  really 
not  ill  but  under-nourished.  This  results  from  caprices  of  appetite,  from 
unfounded  fear  of  injury  from  this  or  that  food  (for  example,  fat  substances), 
from  disturbances  of  appetite  which  are  slight  or  which  are  taken  too  seri- 
ously, from  poverty,  etc.  Thus  they  have  become  accustomed  to  a  too  slight 
ingestion  of  nourishment.  Sometimes  this  is  habitual  from  youth,  and  such 
persons  if  left  to  themselves  never  attain  the  acme  of  nutrition  (muscular 
and  fatty  tissue)  of  which  they  seem  capable,  judging  from  their  constitution 
and  build.  Adipose  tissue  is  scant,  and  the  muscles,  no  matter  how  suscep- 
tible of  development,  and  no  matter  what  efforts  are  made  to  strengthen  them 
by  exercise,  continue  weak,  for  everything  that  is  attempted  is  frustrated  by 
the  oxidation-processes  of  the  body. 

Others  first  manifest  the  symptoms  of  chronic  under-nutrition  after  they 
'have  reached  adult  life.  These  are  mostly  persons  in  whom  there  is  a  neuro- 
pathic taint,  and  in  whom  the  various  forms  of  nervous  dyspepsia  develop. 
Still  others  have  become  neurasthenic  and  hysterical  only  in  the  struggle  for 
existence  against  adverse  circumstances.  Organic  causes  which  would  pre- 
vent a  sufficient  ingestion  of  food  are  not  present,  but  manifold  nervous  dis- 
turbances interrupt  the  distinctive  connection  between  actual  food-require- 
ments (tissue  hunger)  and  appetite  (gastric  hunger).  Gradual  loss  of  weigbt, 
disappearance  of  adipose  and  muscular  tissues,  lessening  of  the  bodily  and 
mental  powers,  are  the  inevitable  consequences.  These  patients,  to  the  detri- 
ment of  their  health,  often  seek  a  cure  by  unsuitable  means,  by  gymnastic 
exercises  and  sports,  by  mountain  climbing,  by  exhausting  cold-water  cures 
(frequently  in  so-called  nature-cure  institutions),  where  they  hope  to  build  up 
their  nervous  system.  This  acts  at  first  like  a  whip,  apparently  increasing 
and  stimulating  their  activities.  But  the  oats  are  lacking,  and  in  a  short 
time  there  is  a  relapse  to  the  former  condition.  The  treatment  is  all  the  more 
harmful  because  the  food,  during  the  time  spent  in  these  exhausting  cures, 
is  weakening  rather  than  strengthening.  The  patients  and  their  "  Natural- 
Healer  "  proceed  from  the  view  that  a  too  profuse  animal  diet  has  disordered 


OCCURRENCE  AND  CONSEQUENCES  OF  OVER-NUTRITION  61 

the  nervous  system.  Meat  and  egg*  are  withdrawn  and  the  patients  are  put 
upon  a  vegetable  diet.  To  this  no  special  objection  can  be  raised,  provided 
it  is  carefully  chosen;  but  too  frequently  it  is  lacking  in  nourishment.  This 
lias  been  so  abundantly  proven  as  to  need  no  further  consideration  at  this  point. 

4.    OCCURRENCE    AND    CONSEQUENCES   OF    OVER-NUTRITION 

If  the  food  (i.  e.,  its  combustion  value)  exceeds  what  is  necessary  for 
maintenance  we  have  the  condition  of  hypernutrition.  In  over-nutrition  the 
organism  does  not  increase  its  processes  of  combustion,  or,  at  least,  does  so 
to  a  very  slight  extent.  Perhaps  the  increase  of  oxidation  which  arises  from 
over-nutrition  has  been  for  a  time  underestimated,  as  the  latesi  investiga- 
tions of  Fr.  Müller  appear  to  prove.  Theoretically  this  increase  is  interest- 
ing, but  it  is  too  slight  to  be  of  practical  importance. 

The  increase  of  oxidation  is  not  due  to  a  stimulation  of  the  cells  to  a  greater 
katabolic  activity,  in  other  words,  to  a  greater  rapidity  of  metabolism,  but 
only  to  the  greater  labor  which  is  put  forth  by  the  mechanism  of  mastication, 
the  stomach  and  intestines,  the  digestive  glands,  the  organs  of  circulation  and 
respiration,  etc.,  in  order  to  work  up  and  utilize  the  greater  mass  of  food. 
After  deducting  the  slight  amounts  spent  upon  the  increased  labor  of  diges- 
tion, etc.  (about  T  per  cent,  to  "20  per  cent,  of  the  energy  supplied  by  the 
food),  a  large  residue  from  the  superfluous  food  remains,  which  accumulates 
as  reserve  material,  and  serves  to  increase  the  body  mass.  We  call  this  "food 
surplus''  (=  the  difference  between  food  ingested  and  food  used  up  in  metab- 
olism). 

Aside  from  slight  differences  it  is  of  no  importance  to  the  processes  of 
metabolism  whether  the  surplus  of  food  occurs  from  excess  of  albuminates  or 
of  N-free  food,  or  whether  the  increased  supply  come-  from  one  source  only 
(the  albumin  or  the  I'at  or  the  carbohydrates).  A  surplus  of  carbohydrate 
nourishment  favors  almost  exclusively  the  production  of  adipose  tissue,  pro- 
dded special  circumstances  do  no!  promote  the  increase  of  protoplasm  (see 
above). 

In  an  especial  case  (B.  K  rug's  experiment  upon  himself  carried  out  under 
my  direction)  the  following  calculations  were  made: 

Dr.  Krug  (perfectly  well  and  in  a  moderately  good  state  of  nutrition), 
after  a  period  in  which  he  had  been  abundantly  nourished,  took  for  fifteen  days 
in  addition  to  his  ordinary  food  a  daily  total  of  1,710  calories,  consisting  of 
fat  and  carbohydrates.  This  sum  represented  "surplus  nourishment";  for 
the  fifteen  days  it  amounted  to  25,650  calories,  of  these  23,05]  calories  were 
utilized  by  the  body. 

1,720  calories  =    7.46  per  cent,  albumin  accumulation,  and 
21,331   calories:    92.54   per  cent,  accumulation  of  fat. 

Whether  the  production  of  albumin  was  equivalent  to  accumulation  of  flesh 

Could    n<>t    he  decided. 

It  follows  from  the  preceding  statements  that  after  the  ingestion  of  a 
surplus  amount  of  food  only  an  accumulation  of  fat  can  certainly  be  counted 


62  OVER-NUTRITION  AND  ÜNDER-NUTRITION 

upon.  It  is  quite  uncertain  whether  an  accumulation  of  muscle  will  take 
place;  with  an  equal  amount  of  surplus  nourishment  the  gain  in  muscle 
varies  from  case  to  case.  It  is  sometimes  lacking,  in  other  cases  it  occurs  to 
a  greater  or  less  extent.  But  it  may  be  prophesied  with  mathematical  cer- 
tainty that  in  over-nutrition  fat  will  accumulate.  How  much  is  dependent 
upon  the  amount  of  food,  and  how  much  upon  the  amount  of  work  performed 
'by  the  body?  A  disproportion  between  the  supply  of  food  and  the  assimila- 
tion of  food,  to  which  the  accumulation  of  fat  (and  ultimately  obesity) 
owes  its  origin,  can  be  brought  about : 

1.  By  an  increase  of  the  food  above  an  average  normal  consumption; 

2.  By  diminution  of  exertion  (muscle  laziness)  with  an  average  normal 
amount  of  food ; 

3.  By  a  combination  of  superfluous  food  and  diminished  exertion. 

We  frequently  meet  with  cases  of  over-nutrition,  but  we  are  not  so  often 
called  upon  professionally  to  combat  this  condition  as  we  are  to  treat  under- 
nutrition. Occasionally,  however,  we  are  called  to  deal  either  with  obesity  or 
with  persons  who,  by  continuing  their  present  mode  of  life,  are  in  danger  of  be- 
coming too  fat.  Every  corpulent  person  has  behind  him  a  period  of  over-nutri- 
tion ;  not,  perhaps,  because  he  has  eaten  more  than  others  who  have  not  become 
fat,  but  he  has  eaten  more  than  his  individual  constitution  and  bodily  func- 
tions enabled  him  to  utilize.  It  is  immaterial  whether  this  superfluous  inges- 
tion of  food  has  arisen  in  consequence  of  a  preference  for  albumin,  for  fat, 
for  carbohydrates,  or  for  alcohol;  we  meet  with  obesity  among  decided  meat- 
and-fat  eaters  as  well  as  among  those  who  prefer  starchy  foods,  sweets,  and 
beer.  We  observe  it  among  those  who  perform  hard  manual  labor,  but  who 
more  than  compensate  for  their  great  metabolism  and  output  of  energy  by  «a 
profuse  intake  of  food ;  we  observe  it  also  in  those  who,  although  they  eat  little, 
consume  an  amount  of  food  out  of  proportion  to  their  slight  physical  activity, 
slight  metabolism  and  slight  output  of  strength.  To  elaborate  this  in  indi- 
vidual instances  would  be  to  consider  the  etiology  and  pathogenesis  of  obesity, 
which  is  not  the  purpose  of  this  article  (the  reader  is  referred  to  my  mono- 
graph on  obesity  in  Nothnagels  Handbuch  der  speciellen  Pathologie  und 
Therapie). 

Whether  in  the  development  of  corpulence  there  is  an  increase  of  the  mus- 
cles depends,  as  we  observe  daily,  upon  external  conditions.  The  rule  holds 
good  that  only  those  obese  persons  who  utilize  and,  in  spite  of  their  corpu- 
lence, exercise  their  muscles  have  strong  and  firm  muscles.  In  such  people 
we  see  the  picture  of  the  so-called  "plethoric  obesity."  Those  who  live  much 
indoors  have  flabby  and  weak  muscles,  often  so  weak  that  serious  consequences 
may  be  the  result.  Distressing  yet  convincing  proofs  are  thus  furnished  to 
show  how  loose  is  the  connection  between  over-nutrition  and  increase  of  muscle. 

5.    INDICATIONS   FOR   HYPERNUTRITION    AND    HYPONUTRITION 

Having  explained  the  changes  of  metabolism  which  occur  in  the  organ- 
ism in  under-nutrition  and  over-nutrition,  we  must  briefly  discuss  the  indi- 
cations for  forced  feeding  and  for  ant i  fat  cures. 


INDICATIONS  FOR  HYPERNUTRITION  AND  HYPONUTRITION         63 


A.     OVER-NUTRITION 

Group  1.  In  chronic  wasting  diseases. — Considered  historically,  over- 
nutrition  in  pulmonary  tuberculosis,  or  rather  in  tuberculosis  of  any  type. 
is  to  be  placed  in  the  front  rank.  Even  the  old  custom  of.  administering  cod 
liver  oil  in  "scrofula"  and  tuberculosis  belongs  to  this  category.  We  have 
gradually  been  forced  to  acknowledge  that  its  action  is  not  specific  bul  due  to 
the  fat  which  it  contains,  that  is,  to  its  high  nutritive  value.  Brehmer  was  the 
first,  and  Dettweiler  the  next,  systematically  to  employ  over-nutrition  in 
tuberculosis.  The  success  of  this  method  is  surprising,  as  anyone  can  see  in  hi- 
daily  experience.  By  over-nutrition,  as  now  carried  out  in  all  institutions 
for  the  cure  of  pulmonary  tuberculosis,  in  hospitals,  in  the  homes  of  the 
patients,  or  wherever  it  may  be  attempted,  we  do  not  attain  a  cure  for  tuber- 
culosis, but  the  favorable  results  which  have  been  attained  up  to  now  in  treat- 
ing tuberculosis  are  inseparably  associated  with  over-nutrition.  Here,  better 
than  anywhere  else,  it  may  be  noted  how  beneficially  the  improvement  in  the 
general  nutrition  acts  upon  the  resistance  of  the  tissues.  I  have  already 
alluded  to  this  elsewhere,  and.  after  further  experience,  I  wish  to  reiterate 
that  the  modern  treatment  of  pulmonary  tuberculosis  by  over-nutrition  is 
in  danger  of  accomplishing  too  much.  Pulmonary  patients  who  had  formerly 
been  emaciated  sometimes  after  treatment  become  corpulent;  this  is  not  to  be 
regarded  as  desirable,  hut  as  a  disadvantage.  For  obesity  always  throw-  in- 
creased work  upon  the  respiratory  and  circulatory  organs,  and  in  this  way 
makes  demands  upon  the  diseased  organ  which  it  should  he  spared.  Bui  apart 
from  these  extreme  cases,  over-nutrition  in  pulmonary  tuberculosis  may  he 
designated  as  one  of  the  mosl  valuable  agents  in  the  realm  of  dietetic  therapy. 

Over-nutrition  as  a  prophylactic  measure  produces  even  more  favorable 
results  than  in  tuberculosis  that  has  already  developed.  It  i-  especially  valu- 
able in  children  and  adolescents  who  have  suffered  from  a  previous  tubercu- 
lous disease  of  the  glands,  joints  and  hones — and  hence  are  Liable  to  a  later 
"pulmonary  tuberculosis " — as  well  as  in  those  who  without  such  preceding 
affections  are  likely  to  become  tuberculous  on  account  of  general  weakness 
am!    hereditary    predisposition.      The    majority    of   consumptives    attacked    in 

the  second  or  third  decades  of  life  have  been,  as  Brehmer  once  correctly  re- 
marked, small  eaters  from  youth,  under  circumstances  such  as  these  the 
early  resori  to  forced  feeding,  combined  with  exercises  to  harden  the  mus- 
cles and  properly  develop  the  body,  is  one  of  the  mosl  beneficent  and  grateful 
tasks  of  the  family  physician,  all  the  more  grateful  if  tin-  method  be  insti- 
tuted early  in  life  when  the  body  i-  -till  in  the  Btage  of  growth  and  the 
accumulation  of  muscular  tissue  take-  place  more  readily  than  in  later  years. 
Cure-  based  <>n  forced  feeding  practically  play  a  leas  important  role  in 
all  other  chronic  wasting  diseases  than  in  tuberculosis.  Mosl  Important,  per- 
haps, is  over-nutrition  in  syphilis,  a  disease  which  frequently,  ;in.l  especially 
in  its  early  stages,  markedly  influences  nutrition,  and  in  it<  subsequenl  course 
(in  the  so-called  tertiary  form-)  almo-t  invariably  produces  extensive  fciasue- 
disintegration.    The  old  custom,  originating  centuries  ago,  and  not  wl  rooted 

out,  was  to  place  these  patient-  upon  a  -cant,  meager  diet,  and  to  weaken  them 


64  OVER-NUTRITION  AND  UNDER-NUTRITION 

by  laxative  drinks.  In  contrast  to  these  old  usages,  an  excessive  or  forced 
administration  of  nourishment  has  shown  itself  to  be  much  more  efficacious. 
Many  protracted  cases  of  tertiary  syphilis  can  be  cured  only  when  the  body 
has  been  thus  strengthened  by  over-nutrition. 

Diabetes  mellitus  may  also  be  counted  among  the  chronic  wasting  diseases, 
naturally  within  certain  limitations,  as  there  are  numerous  cases  of  diabetes 
mellitus  in  which,  vice  versa,  definite  relations  to  obesity  exist.  Where  this 
is  not  the  case  (as  in  the  severe  forms  of  diabetes,  particularly  that  occurring 
in  youth),  emaciation  is  combined  with  the  disease,  partly  as  the  result  of 
losses  in  sugar,  and  partly  as  the  result  of  peculiarities  of  the  diet,  To  inter- 
fere, to  replace  by  over-nutrition  not  only  what  has  been  lost  and  if  possible 
to  raise  the  patient's  state  of  nutrition  above  the  average,  is  important,  for 
experience  teaches  that  a  good  state  of  nutrition  will  often  avert  many  of  the 
dangers  of  the  disease. 

Diabetes  insipidus  must  also  be  mentioned.  Unfortunately,  we  know 
little  regarding  the  pathogenesis  and  the  minute  disturbances  of  metabolism 
which  take  place  in  this  disease.  The  most  conspicuous  symptom  in  all  severe 
cases  is  the  decided  emaciation  and  loss  of  strength,  which  cannot  be  reason- 
ably explained  from  the  loss  of  water  by  the  body.  If  we  leave  out  of  con- 
sideration the  gradual  restriction  of  the  intake  of  water,  and  a  few  purely 
symptomatic  drug  indications,  the  especial  and  systematic  improvement  of 
the  nutrition  by  a  long-continued,  forced  diet  is  the  only  measure  which 
promises  success.  In  view  of  the  rarity  of  these  cases,  I  shall  briefly  report 
a  case  under  treatment  by  me  three  years  ago  for  diabetes  insipidus.  The 
disease  occurred  in  a  man  aged  fifty,  and  was  credibly  reported  to  have  fol- 
lowed a  severe  shock  sustained  in  a  railway  accident ;  it  had  existed  for  about 
fifteen  months.  The  patient's  previously  normal  state  of  nutrition  had  suf- 
fered acutely  during  this  time,  the  loss  in  weight  amounting  to  more  than 
25  kilograms.  The  daily  amount  of  urine  varied  between  9  and  13  liters.  In 
this  case,  by  a  plentiful  addition  of  cream  and  butter  to  his  diet  (between  250 
and  300  grams  of  milk  fat  daily),  weight  was  increased  20  kilograms  within 
four  months.  After  the  first  six  weeks,  the  urine  had  already  diminished  to 
between  5  and  6  liters,  and,  after  two  months  more,  to  3  to  4  liters.  The  once 
markedly  debilitated  patient  had,  in  the  mean  time,  become  strong  again  and 
fully  capable  of  working.  He  continued  strong  until  attacked  the  following 
winter  by  pneumonia  to  which  he  succumbed.  According  to  the  statements 
of  his  relatives  there  had  been  no  increase  in  the  amount  of  urine. 

Finally,  among  the  chronic  wasting  diseases,  we  must  mention  exoph- 
thalmic goiter  (Basedow's  disease).  Probably  from  a  thyreogenous  auto- 
intoxication (Möbius,  Fr.  Müller,  A.  Magnus-Levy)  an  increase  of  the  proc- 
ess of  metabolism  occurs,  i.  e.,  an  increase  both  in  the  assimilation  of  albumin 
and  in  the  combustion  of  fat.  In  consequence  of  this,  if  the  patients  take 
only  the  amount  of  food  which  is  the  average  for  normal  persons,  this  proves 
insufficient,  and  they  therefore  consume  their  own  body  substance  (protoplasm 
and  fat).  Only  by  over-nutrition  can  we  safeguard  them  from  this.  By  over- 
nutrition  it  is  possible  at  least  to  conserve  the  fat,  or  we  may  even  hope  to 
increase  it.     According  to  the  researches  of  Fr.  Müller,  we  cannot  count  on 


INDICATIONS  FOR  HYPERNUTRITION  AND   HYPONUTRITION  65 

maintaining  and  developing  the  muscular  tissue  even  by  forced  feeding  so 
long  as  the  disease  progresses.  Nevertheless,  forced  feeding  carried  on  per- 
sistently is  remarkably  successful;  the  patients  accumulate  valuable  reserve 
material,  and  experience  shows  that  they  are  much  better  than  when  exposed 
to  progressive  emaciation  by  dietetic  negligence.  But  though  it  is  necessary 
to  promote  the  nutrition  of  the  patient,  it  is  not  to  be  supposed  that  a  very 
energetic  and  rapid  forced  feeding  is  here  indicated.  Great  care  is  neces- 
sary; for  patients  who  present  severe  forms  of  Graves'  disease,  and  whose 
nutritive  condition  has  been  correspondingly  damaged,  suffer  also  from  car- 
diac weakness.  To  maintain  their  balance  of  nutrition,  they  require  upon 
the  average  from  15  to  20  per  cent,  more  food  than  a  person  in  normal  health 
of  the  same  weight  and  build,  and  of  course  if  we  are  to  attain  an  increase  in 
weight,  still  more  food  is  necessary.  But  according  to  my  experience,  the 
cardiac  difficulties  frequently  increase  if  we  proceed  too  rapidly  with  forced 
feeding.  Indeed  the  cardiac  weakness  which  results  may  he  dangerous.  Last 
year  an  able  author  reported  a  case  in  which,  in  a  short  time,  an  increase  of 
weight  of  22  pounds  was  brought  about  by  over-nutrition.  In  spite  of  this 
desirable  result,  collapse  occurred  in  which  the  patient  succumbed.  I  believe 
it  cannot  be  doubted  that  this  too  rapid  over-nutrition  was  responsible  for 
the  unfavorable  outcome.  I  have,  myself,  not  seen  such  serious  results  from 
over-nutrition  in  Basedow's  disease,  but  I  have  observed  exacerbations  which 
made  me  fear  collapse.  Hence,  there  is  need  of  proceeding  slowly  in  all 
severe  cases;  we  must  be  satisfied  if  at  first  only  the  rapid  loss  of  weight  is 
stopped.  When  this  has  been  accomplished,  and  the  weight  maintained  for 
several  weeks,  forced  feeding  should  be  again  resorted  to.  but  an  increase  of 
abouf  a  pound  a  week  should  not  be  exceeded. 

Group  2.  In  functional  nervous  diseases. — We  are  indebted  to  S.  Weir 
Mitchell  for  having  pointed  out  the  deleterious  effects  in  neurasthenic  and  hys- 
terical pel-sons  of  a  poor  state  of  nutrition — whether  this  dated  from  the  onset 
OT  developed  in  the  course  of  the  disease,  lie  still  further  demonstrated,  by 
innumerable  and  convincing  examples,  that  with  systematic  over-nutrition 
(forced  feeding)  not  only  the  state  of  the  nutrition  hut  also  the  activity  of 
the  nervous  Bystem  could  he  restored. 

Nearly  twenty  years  have  passed  since  the  publication  of  these  view-  by  S. 
Weir  Mitchell  and  since  that  time  forced  feeding  in  the  treatment  of  neura- 
hhenia  and  hysteria  has  become  the  common  method  of  nearly  all  physicians. 
The  results  thus  attained  are  the  foundation  and  the  corner  stone  of  the 
reputation  which  numerous  clinics  and  sanatoria  have  acquired  in  the  treat- 
ment of  these  cases.  Retrospectively  speaking,  this  therapeutic  accomplish- 
ment which  we  owe  to  S.  Wei)-  Mitchell  is  of  the  highest  significance.  The 
treatment  of  Weir  Mitchell  and  Playfair,  the  latter  of  whom  did  a  greal 
deal  to  popularize  the  method,  consists  of  several  factors: 

1.    Isolation  of  the   patient. 

'l.  Rest   in  bed,  lasting  according  to  the  ein  u instances  of  the  case  from 

one  to  several    weeks. 

:i.  Over-nutrition ;  beginning  with  .-mall  amounts  of  food,  and  gradually 
increasing  to  high  values, 
c» 


66  OVER-NUTRITION  AND  UNDER-NUTRITION 

•i.  Massage  and  faradization  of  the  muscles  during  the  rest  in  bed ;  careful 
hydrotherapy  to  stimulate  the  circulation. 

For  numerous  cases,  especially  those  in  which  excessive  irritability  of  the 
nervous  system  is  prominent  among  the  clinical  symptoms,  no  more  valuable 
treatment  can  be  outlined  to-day  than  the  Weir  Mitchell-Playfair  plan.  But 
it  has  been  demonstrated  that  the  diversity  of  the  cases  necessitates  numerous 
modifications.  The  other  factors  associated  with  hypernutrition  (especially 
isolation,  rest  in  bed,  massage,  etc.)  are  frequently  not  only  unnecessary,  but 
actually  a  hindrance  to  success.  The  diet  which  Weir  Mitchell  proposed  may 
be  modified  as  occasion  requires.  Any  one  conversant  with  the  laws  of  nutri- 
tion and  with  general  therapy  may  with  ease  select  what  is  suitable  for  each 
individual  case. 

My  experience  leads  me  to  state  that  I  frequently  employ  only  limited 
isolation,  i.  e.,  the  removal  of  the  patient  from  his  usual  surroundings  and 
activities,  but  rarely  insist  on  prolonged  rest  in  bed.  In  my  opinion,  the 
latter  should  be  avoided  whenever  possible,  for  reasons  previously  men- 
tioned. 

The  indications  for  forced  feeding,  according  to  the  experiences  of  the 
last  twenty  years,  are  present  in  functional  neuroses  combined  with  mal- 
nutrition, whether  the  poor  state  of  nutrition  is  to  be  looked  upon  as  the 
cause  of  the  neurosis,  or  whether  the  neurosis  by  its  influence  on  the  intake 
of  nourishment  and  digestive  processes  produces  secondarily  a  damage  to  the 
nutrition  of  the  body.  In  the  former  case,  we  can  well  hope  to  remove  all  of 
the  pathologic  phenomena  together  with  their  cause.  In  the  latter  case  we 
are  at  least  combating  a  symptom  from  which  the  disease  constantly  receives 
new  stimulus. 

Here  also,  as  in  the  case  of  exophthalmic  goiter — although  not  for  the 
same  reasons — I  must  caution  against  immoderation.  Many  neurasthenics  are 
easily  fattened,  and,  after  six  to  seven  weeks,  may  show  a  gain  of  30  or  40 
pounds  in  weight.  But  during  such  rapid  augmentation  of  body-weight  new 
disturbances  not  infrequently  appear  which,  in  themselves  unimportant,  are 
over-estimated  and  exaggerated  by  the  suspicious  neurasthenic  and  hysterical 
patient.  For  this  reason,  I  limit  the  acquisition  of  weight  desired  to  about 
20  pounds,  which,  according  to  the  individual  case,  may  take  from  four  to 
five  weeks.  Then  a  halt  must  be  called,  and  after  an  interval,  forced  feeding, 
if  necessary,  may  be  begun  again. 

Group  3.  In  all  individuals  with  a  poor  condition  of  nutrition  it  is  im- 
portant to  determine  whether  this  faulty  nutrition  has  been  the  hindrance 
to  the  full  development  of  their  power,  to  the  natural  building  up  of  their 
bodies  (in  children  and  young  persons),  to  recuperation  after  excessive  bodily 
and  mental  labor,  or  to  convalescence  after  diseases.  The  guide  for  the  physi- 
cian must  be  not  only  the  present,  but  the  thought  of  what  the  future  may 
bring.  The  various  special  indications  cannot  be  individually  described  with- 
out entering  into  the  wide  realm  of  general  pathology.  I  should  like  to 
repeat  (see  above)  that  for  every  person  there  is  a  different  optimum  of 
nutrition.  Only  experience  will  enable  the  physician  to  estimate  and  recog- 
nize this  optimum  in  individual  cases.    He  who  trains  himself  from  this  point 


INDICATIONS   FOR  HYPERNUTRITION  AND  HYPONUTRITION         67 

of  view  possesses  weapons  against  disease  (existing  and  threatening)  than 
which  there  are  none  more  effective 

Of  course  in  all  of  these  cases,  even  more  than  in  Groups  1  and  2,  the 
development  of  the  muscles  must  be  considered,  for  by  the  accumulation  of 
fat  alone  nothing  is  gained.  Therefore,  systematic  muscular  exercise  must 
be  added  to  forced  feeding.  The  form  which  this  exercise  takes  is  of  minor 
importance.  I  prefer  exercise  in  the  open  air  (walking,  mountain  climbing, 
gymnastic  exercises,  games,  bicycling,  etc.),  provided  we  are  certain  of  not 
overdoing,  to  massage  or  indoor  gymnastics.  Gymnastics  with  apparatus 
deserve  consideration  only  when  exercise  in  the  open  air  is  contra-indicated 
for  special  reasons,  or  when  development  of  special  muscle  groups  is  desirable. 

As  a  rule,  it  is  wise  to  regulate  forced  feeding  and  muscular  exercise  in 
this  third  group  of  cases,  so  that  only  a  gradual  increase  of  weight  results. 
We  are  then  much  more  certain  of  a  permanent  and  substantial  gain.  In 
cases  belonging  to  the  first  and  second  group,  increases  in  weight  of  about 
L2  to  15  pounds  within  four  weeks — with  certain  exceptions  (see  above) — are 
worth  striving  for,  and  sometimes,  as  in  neurasthenics,  particularly  rapid 
results  are  important  as  suggestive  curative  agents.  But  in  cases  of  the  third 
group  it  is  better  to  have  this  increase  in  weight  distributed  over  months 
instead  of  weeks.  From  this  it  may  be  further  concluded  that  these  persons, 
who  need  not  so  much  an  instant  recovery  from  a  morbid  condition  as  a  general 
strengthening  of  the  body,  should  not  be  treated  in  hospitals  or  Sanatoriums, 
or  (inly  temporarily.  Few  can  bear  removal  from  the  ordinary  routine  of  daily 
life  for  so  long  a  time,  for  the  air  of  the  sanatorium  is  rich  in  psychical  con- 
tagion. The  treatment,  and  especially  the  regulations  for  forced  feeding  and 
slow  increase  of  the  body-weight,  must  therefore  be  planned  according  to  the 
patient's  circumstances,  occupation,  habits,  and  position  in  life.  With  strict 
regulations  we  are  less  likely  to  reach  our  goal  than  if  the  constraint  of  an 
institution  is  abolished.  Of  course  a  complete  change  from  the  previous  mode 
of  life  which  led  to  the  unsatisfactory  condition  is  the  first  stop.  Then  we 
i  an  easily  learn  whether  a  simple  increase  of  food  without  any  special  regula- 
tion of  its  quality,  quantity  or  distribution  is  sufficient,  or  whether  any  par- 
ticular food  must  be  added  to  the  diet  to  make  the  success  certain,  and,  lastly, 
whether  this  addition  should  come  from  the  albumin  group,  from  fats  or 
from  carbohydrates. 

B.     UNDER-NUTRITION 

Antifat  cures  are  undertaken  almost  exclusively  in  obese  persons;  rarely. 
if  ever,  in  persona  normally  or  insufficiently  nourished.  What  rule  is  to 
guide  the  physician  in  the  important  problem:  Is  an  aniil'at  cure  t<>  he  begun 
"i-  not?  I  desire  to  refute  the  opinion  so  frequently  expressed  that  antifat 
cures  always  belong  to  the  so-called  "  weakening  cures/5  The  popular  views 
in  regard  to  this  are  very  exaggerated.  I  maintain  positively  that  an  anti- 
fat  cure  begun  for  proper  reasons — and  provided  that  the  choice  of  the 
method,  the  rapidity  with  which  it  is  carried  out.  and  the  loss  of  weight  are 
adjusted  to  the  individual  condition — never  deserves  the  name  of  a  "  weaken- 
ing cure,"  hut  may  always  be  conducted  without  injury  to  the  patient,  and 


ßg  OVER-NUTRITION  AND  UNDER-NUTRITION 

will  always  be  beneficial  to  the  whole  body.  It  will  be  noted  that  this  favorable 
opinion  is  based  upon  a  number  of  provisos  which,  although  apparently  sim- 
ple, require  careful  consideration  and  good  judgment. 

I  shall  mention  only  the  most  important  of  the  indications  as  these  have 
been  elsewhere  extensively  discussed.1 

1.  Simple  obesity  in  otherwise  healthy  persons. —  (a)  Extreme  obesity  is 
almost  always  an  indication  for  an  antifat  cure.  The  dangers  which  may 
result  from  a  further  gain  of  fat  are  great,  and  we  must  endeavor  to  prevent 
them.  Certain  modifications  are  required  by  the  age  of  the  patient.  In  chil- 
dren and  in  adolescents  up  to  about  the  twentieth  year,  we  should  be  content 
with  preventing  an  extreme  development  of  obesity,  and  only  from  time  to 
time,  during  short  periods  of  from  four  to  five  weeks,  should  an  effort  be  made 
to  reduce  the  superfluous  fat  (intermittent  antifat  cures).  In  the  aged  antifat 
cures  are  prohibited,  as  almost  invariably  there  is  a  rapid  loss  of  strength. 

(h)  Moderate  obesity  (body-weight  about  15  to  25  kilograms  above  the 
average  for  the  age,  sex  and  height)  is  most  frequent  and  at  the  same  time 
best  suited  for  treatment.  In  most  cases  it  can  be  let  alone  without  any  great 
danger  to  health,  but  it  cannot  be  denied  that  corpulence  brings  many  evils 
in  its  train;  for  if  any  acute  disease  occurs  (infections,  diseases  of  the  heart, 
of  the  lungs,  of  the  kidneys,  the  joints,  etc.)  or  after  unusual  exertion  (such 
as  over-strain  of  the  heart)  the  obesity  may  become  dangerous.  Here,  also, 
the  rule  holds  that  in  the  aged  this  treatment  must  not  be  attempted,  and 
in  childhood  and  in  youth  only  in  slow  tempo  and  with  the  greatest  caution. 

(c)  Slight  obesity  (body- weight  upon  the  average  5  to  15  kilograms  above 
the  normal)  in  healthy  persons  never  necessitates  an  antifat  cure,  but,  if  the 
corpulence  steadily  increases,  measures  may  be  taken  to  check  its  further 
development.  Nevertheless,  very  often,  particularly  in  women,  the  aid  of  a 
physician  is  sought  because  of  a  desire  to  reduce  weight  and  to  attain  slen- 
derness.  In  many  cases  the  physician  will  all  the  more  willingly  comply 
with  the  wishes  of  his  patients  as  he  may  thus  gain  control  of  their  entire 
mode  of  life,  in  which  usually  much  should  be  amended.  Although  in  the 
effort  to  reduce  early  obesity,  and  in  the  timely  regulation  of  detrimental 
habits,  vanity  rather  than  bodily  ill  is  sometimes  the  motive  power,  we  as 
physicians  should  not  criticise  this.  It  may  amuse  us,  but  it  must  be  wel- 
comed as  a  therapeutic  opportunity. 

Care  is  always  necessary.  Many  a  woman,  as  the  result  of  a  too  rapid  and 
too  far  reaching  antifat  cure,  acquires  in  exchange  for  her  moderate  corpulence 
various  derangements  of  the  abdominal  organs,  such  as  constipation,  ruptures, 
gastrectasis,  movable  kidney,  sometimes  also  of  the  uterus;  or,  after  the  dis- 
appearance of  fat,  the  liver  and  gall-bladder  are  more  exposed  to  the  pressure 
of  the  corset,  the  flow  of  bile  is  impeded,  and  gall-stones  result.  All  these 
evils  are  much  more  frequent  in  slight  corpulence  than  when  it  is  marked. 
In  the  latter  the  antifat  treatment  is  rarely  carried  to  such  an  extent  that 
decided  pressure  changes  occur  in  the  abdominal  cavity;  enough  fat  always 
remains  to  protect  the  viscera  and  preserve  them  from  injury. 

i  v.  Noorden,  "  Sammlung  klinischer  Abhandlungen,"  Heft  1,  Berlin,  1900. 


THE  TECHNIC  OF  OVER-NUTRITION  AXD  UNDER-NUTRTTION        69 

It  mav  be  said  in  general  that  slight  obesity  does  not  especially  demand 
slow  and  careful  reduction  of  weight,  although,  to  prevent  excessive  corpulence 
ami  for  many  other  reasons,  this  is  often  very  desirable. 

2.  Indications  for  antifat  cures  when  obesity  is  complicated  by  other 
diseases. — Diseases  of  various  kinds,  from  slight  functional  disturbances  of 
vital  organs  to  severe  anatomical  changes,  may  influence  the  physician  in  his 
decision  of  the  antifat  question.  More  frequently  than  otherwise,  it  is  the 
complicating  conditions  that  we  meet  which  lead  us  to  combat  obesity. 

Such  complications  may  lead  us  to  undertake  an  antifat  cure  when  if  we 
found  a  normal  condition  of  all  the  organs  there  would  be  no  indication  for 
treatment. 

Among  the  disturbances  whose  course  and  prognosis  are  influenced  by 
obesity,  and  which  for  this  reason  may  necessitate  the  reduction  of  moderate 
and  even  slight  corpulence  are  the  following: 

Disturbances  of  the  organs  of  circulation,  such  as  valvular  diseases,  myo- 
carditis, myocardiac  degeneration  of  the  heart,  fatty  heart,  or  better,  cardiac 
weakness  in  obesity,  arteriosclerosis,  aortic  aneurism,  etc. 

Renal  diseases,  particularly  contracted  kidney,  on  account  of  the  implica- 
tion of  the  heart  and  the  arteries  which  is  always  associated  witb  it. 

(  ertain  chronic  diseases  of  the  respiratory  organs,  such  as  chronic  bron- 
chitis, pulmonary  emphysema,  extensive  bronchiectases,  bronchial  asthma. 
adhesive  pleurisy:  kyphoscoliosis  also  may  be  here  included. 

Chronic  articular  rheumatism. 

Gout  in  all  severe  forms. 

Other  diseases  characterized  by  loss  or  difficulty  of  motion  or  locomotion. 
for  example,  hemiplegias,  chronic  diseases  of  the  spinal  cord,  «uue  cases  of 
peripheral  paralysis,  many  surgical  affections  of  the  hones  and  joints,  large 
varices,  chronic- ulcer  formation  upon  the  leg.  deformities  of  the  lower 
extremities,  etc. 

Diseases  of  the  nervous  system.  That  neurasthenics  and  hysterical  per- 
sons  in  general  are  in  better  condition  when  their   fat    is  somewhat   profusely 

developed  has  already  1 o  mentioned:  therefore  these  are  the  patients  who 

frequently  require  forced  feeding  (see  above).  Bui  as  these  neuroses  do  not 
always  disappear  under  forced  feeding,  neither  does  corpulence  always  pre- 
\ent  their  appearance.  Where  the  neurosis  is  combined  with  corpulence,  care- 
ful antifal  treatment  and  the  ro-estahlishnient  of  the  normal  nutritive  con- 
dition mav  he  indicated,  ami  mav  he  as  potent  in  relieving  the  neuro-i-  as 
forced  feeding  is  in  thin,  poorly  nourished  persons. 

6.    REMARKS    REGARDING    THE    TECHNIC    OF    OVER-NUTRITION 
AND     UNDER-NUTRITION 

Tl  is  an  old  axiom  which  constantly  demonstrates  itself  anew  that  dietetic 

cures  originating  with  this  or  that  author,  and  advised   for  this  or  that  disease, 

degenerate  in  practice  into  mere  formulae.    The  •■cure.*'  the  method.  i<  forced 

upon  the  patient,  instead  of  the  method  being  adjusted  to  the  patient  and  it- 
main  principles  applied  to  the  unending  variety  of  cases.     Routine  precludes 


70  OVER-NUTRITION  AND  UNDER-NUTRITION 

success  in  this  field,  and  frequently  does  more  harm  than  good.  There  is  no 
single  "  best  method "  of  over-nutrition,  and  no  single  best  method  for  the 
removal  of  fat,  but  there  is  for  each  individual  case  one  and  only  one  best 
method.  It  must  be  constructed  by  the  physician  upon  the  scientific  laws  of 
nutrition,  whether  a  celebrated  name  is  attached  to  the  method  or  not.  Hard 
and  fast  dietetic  rules  are  most  widely  developed  in  the  realm  of  antifat  cures. 
There  are  obesity  cures  according  to  Harvey-Banting,  Oertel,  Ebstein,  Hirsch- 
feld, Schweninger,  Kisch,  Pastor  Kneipp,  etc. 

I  do  not  intend  either  in  over-nutrition  or  in  under-nutrition  to  dwell 
upon  the  individualities  of  the  methods,  but  I  shall  emphasize  the  main  points. 

A.    THE   TECHNIC   OF  FORCED   FEEDING 

Over-nutrition  presupposes  that  the  ingestion  of  food  is  to  be  greater 
than  the  requirement.  How  great  the  surplus  of  food  is  to  be  depends  upon 
the  rapidity  with  which  the  process  is  to  be  carried  out.  Apart  from  particu- 
lar indications  (for  example,  in  Graves'  disease,  see  above)  the  capacity  of  the 
digestive  organs  should  decide  this  question. 

How  the  requirements  of  the  patient  can  be  approximately  determined 
from  the  body-weight  has  been  related. 

According  to  the  calculations  which  I  made  in  a  large  number  of  cases 
treated  by  forced  feeding  I  obtained  the  following  results  (I  must  admit  in 
this  connection  that  the  figures  had  not  been  theoretically  determined  prior 
to  beginning  forced  feeding,  but  were  gained  empirically  during  the  treat- 
ment) :  With  a  daily  excess  of  food  of  about  500  to  800  calories,  we  get  an 
increase  of  weight  of  from  600  to  1,000  grams  in  a  week;  with  a  daily  in- 
crease in  food  of  800  to  1,200  calories,  weight  increases  from  800  to  1,200 
grams  per  week;  with  a  daily  excess  of  food  of  from  1,200  to  1,800  calories, 
weight  increases  from  1,200  to  2,000  grams  per  week. 

Quite  properly  the  question  arises,  not  only  how  many  calories  should  the 
food  contain,  but  also  how  much  albumin  and  X-free  substances  are  included 
in  it. 

The  albumin  bodies  theoretically  considered  have  no  great  value  in  in- 
creasing weight.  The  average  albumin  content  of  ordinary  diet  (100  to  110 
grams)  may  be  somewhat  increased  in  forced  feeding,  but  hardly  more  than 
50  grams.  Still  larger  quantities  of  albumin  can  be  utilized  only  in  excep- 
tional cases  as  the  bulk  of  the  food  becomes  too  great,  and  also  because  all 
albuminous  foods  produce  satiety  to  a  marked  extent.  Even  the  preparation 
of  purified  albumin  products  (casein,  nutrose,  tropon,  plasmon,  roborat,  aleu- 
ronat,  ergon,  etc.)  has  not  changed  this.  From  20  to  30  grams  during  the 
day  are  useful ;  larger  quantities,  if  their  use  be  prolonged,  as  a  rule  spoil  the 
appetite,  whether  we  administer  them  in  milk,  soups,  sauces,  pap,  in  the  form 
of  pastry  or  otherwise.  No  matter  to  what  form  we  add  the  50  grams  of  albu- 
min, which  I  have  designated  as  the  most  that  can  be  used,  it  is  certain  that  for 
increase  of  weight  little  is  gained  by  this;  it  only  furnishes  about  205  calories. 

I  hold  that  in  general,  allowing  for  exceptions,  the  daily  administration 
of  from  120  to  130  grams  of  albumin  is  quite  sufficient.  My  best  results 
were  arrived  at  by  keeping  within  these  limits.     Nevertheless,  it  must  be 


THE  TECHXIC  OF  OVER-NUTRITION  AND  UNDER-NUTRITION       71 

emphasized  that  occasionally  the  mere  increase  of  the  amount  of  albumin  is 
beneficial;  for  example,  in  preparation  for  true  forced  feeding,  or,  if  there  is 
repugnance  to  great  quantities  of  N-free  food,  during  a  "  vacation  period  "  of 
from  eight  to  fourteen  days  which  the  patient  may  have  to  take  in  his  forced 
feeding  treatment.  Under  these  conditions  temporary  forcing  of  the  albumin- 
intake  at  the  expense  of  the  X-free  substances  renders  the  body  more  receptive 
to  the  later  action  of  the  true  forced  feeding.  For  these  purposes  the  purified 
albumin  preparations,  such  as  plasmon,  etc.,  are  more  suitable  than  meat. 
From  50  to  GO  grams  of  plasmon  may  be  given  with  advantage  during  the 
day.  Tbcre  is  no  difficulty  in  administering  this  amount,  as,  in  this  period, 
we  no  longer  increase  the  N"-free  Mihstance.  During  longer  periods,  however, 
little  can  be  expected  from  such  an  exclusive  increase  of  the  albuminates. 

Among  the  substances  free  from  nitrogen  we  may  choose  between  the 
administration  of  fats  or  of  carbohydrates,  or  may  administer  both  in  almost 
equal  proportions.  In  principle  it  is  immaterial,  as  fat  and  carbohydrates 
compensate  for  one  another  according  to  the  law  of  isodynamics.  One  hun- 
dred grams  of  fat  are  equal  to  224  grams  of  carbohydrates,  and  vice  versa. 
As  a  rule  the  marked  increase  of  carbohydrates  is  preferable,  provided  always 
that  they  are  better  tolerated  than  fats.  In  some  patients  this  is  unquestion- 
ably true,  but  in  the  majority  certainly  not.  If  we  desire  to  add  about  1,200 
calories  of  X-free  substances,  we  require  either  129  grams  of  fat  or  300  grams 
of  carbohydrate- ;  many  other  mixtures  may  be  used;  for  example,  ''oil  grains 
of  carbohydrates  and  40  grams  of  fat,  or  ]<><>  grams  of  carbohydrates  ami  8S 
grams  of  fat. 

For  more  than  ten  years  I  have  preferred  to  Increase  the  administration 

of  fat,  for  I  have  found  that  a  larger  amount  of  earbohydrat» 300  to  400 

grams  a  day — is  not  well  borne  for  any  length  of  time.  When,  under  the 
constraint  of  treatment  in  an  institution,  the  patient  is  forced  to  take  the 
large  amounts  of  food  which  an'  necessary  if  we  use  the  carbohydrates  alone, 
we  see  only  too  frequently,  after  the  restraint  is  removed,  a  period  of  anorexia 
during  which  much  of  the  body-weighl  gained  with  so  much  difficulty  is  lost. 

Accordingly,  the  composition  of  tin'  nourishment  during  forced   feeding 

should  he  about   a-  follow-  ; 

120  to  130  gram-  of  albumin   t  190  to  530  calories). 

300  to  ."-mi  -ram-  of  carbohydrate   (1,230   to   1,435  calories). 

Tin-  noiiri-hment  (720  to  1,965  calorie-)  form-  the  ba-i-  to  which  as 
much  fat  may  lie  added  a-  i-  necessary  to  make  the  proposed  calory  total: 
i.e..  from  800  to  300  grams  of  fat  (1,860  to  2,730  calories)  or  even  more. 
Frequently  a  portion  of  the  required  calory  excess  may  be  given  in  the  form 

Of  alcohol,  whereby  certain  amount-  of  fat  are  protected  from  oxidation  and 
preserved  f,,y  tin'  organism  (!»..'!  gram-  of  alcohol  proteel  about  J  gram-  of 
fat  from  oxidation). 

The  amount  of  water  to  he  added,  provided  special  indication-  do  not 
necessitate  exact  regulation,  may  he  according  to  the  desire  of  the  patient. 
A-  a  rule,  if  much  carbohydrate  Is  ,Lri\en  the  amount  i-  greater  than  if  much 
fat  i-  administered. 


72 


OVER-NUTRITION  AND  UNDER-NUTRITION 


B.    THE   TECHNIC   OF   ANTIFAT   CURES 

In  antifat  cures  the  intake  of  nourishment  must  be  smaller  than  the 
demand,  and  in  the  obese  this  cannot  be  estimated  very  readily.  The  practi- 
cal need  will  be  satisfied  if  for  an  obese  person  the  average  normal  require- 
ment, amounting  to  about  2,500  calories,  is  given  and  is  combined  with  slight 
or  moderate  bodily  exertion.  On  this  basis  I  have  proposed  the  following 
scale  in  antifat  cures : x 

First  grade  of  antifat  diet. — To  this  belong  antifat  cures  in  which  the 
diet  may  be  reduced  to  about  four-fifths  of  the  normal  requirement,  i.  e.,  to 
about  2,000  calories.  Success  follows  this  only  when  we  are  treating  robust 
persons  who  are  able  to  take  sufficient  bodily  exercise.  The  action  is  usually 
slow;  we  must  not  count  in  the  beginning  upon  losing  more  than  from  three 
to  four  pounds,  and  later  two  to  three  pounds,  of  weight  per  month. 

Second  grade  of  antifat  diet. — In  this  category  the  antifat  cures  belong 
in  which  the  diet  is  reduced  to  three-fifths  of  the  usual  requirement,  there- 
fore, to  about  1,400  to  1,500  calories.  This  diet  may  very  readily  be  adapted 
to  the  mode  of  life  of  most  patients,  so  that  they  can  follow  their  occupations 
without  hindrance.  The  rapidity  of  cure  depends  upon  the  amount  of  physical 
exercise  they  can  take.  If  exercise  is  difficult  or  impossible  (as  in  many 
women,  in  very  lazy  persons,  in  certain  diseases,  particularly  in  paralysis  and 
with  threatening  signs  of  cardiac  weakness),  the  action  of  diet  alone  is  quite 
slow  (about  two  to  three  pounds  a  month).  In  vigorous  persons  who,  besides 
pursuing  their  daily  occupations,  can  devote  an  hour  to  an  hour  and  a  half 
daily  to  mountain  climbing,  bicycling,  rowing,  exercise  in  the  gymnasium,  etc., 
at  first  losses  in  Aveight  of  four  to  six  pounds,  later  of  two  to  four  pounds,  a 
month  are  the  result.  For  a  time,  as  for  instance  during  a  vacation  in  the 
mountains,  these  losses  may  without  excessive  exertion  be  increased  to  11 
pounds  a  month  or  more. 

Third  grade  of  antifat  diet. — To  this  belong  antifat  cures  in  which  the 
diet  is  less  than  three-fifths,  or  even  only  two-fifths  of  the  usual  requirement, 
i.  e.,  about  1,000  to  1,400  calories.  In  this  class  belong  the  well-known  diet- 
aries calculated  to  produce  decided  and  rapid  action,  those  of  Banting-Harvey, 
Oertel,  Ebstein,  and  others,  as  is  shown  by  the  following  tables : 


Diet  Scheme  according  to 


j  Maxi 
(  Minii 


aximum. 

inmm  . 


Banting . . . 
Oertel 
Ebstein  .  . . 
Hirschfeld 


Kisch j  Plethoric  obesity. 

(  Anemic  obesity  . . 
v.   Noorden 


(  Maximum. 
/  Minimum  . 


Albumin. 


172 
170 
156 
102 
139 
100 
160 
200 
155 


Carbo- 
hydrates. 


81 

120 

75 

47 

67 

50 

80 

100 

112 


Fat. 


45 
25 
85 
65 
41 
11 
12 
28 


Calories. 


1,100 
1,600 
1,180 
1,300 
1,400 
1,000 
1,086 
1,116 
1,366 


i  v.  Noorden,  "  Die  Fettsucht  "  in  Nothnagel's 
und  Therapie,"  Wien,  1900,  p.  110. 


Handbuch  der  speciellen  Pathologie 


THE  TECHXIC  OF  OVER-NUTRITION  AND  UNDER-NUTRITION        73 


A  diminution  of  food  to  about  two-fifths  of  the  usual  requirement  is 
looked  upon  as  the  utmost  that  may  be  wisely  attempted  in  the  obese  patient. 
The  amount  and  rapidity  of  the  loss  of  weight  depend  in  the  main  on 
the  accompanying  conditions.  If  the  patient  is  inactive,  the  loss  in  weight 
amounts  to  from  6|  to  13  pounds  in  a  month.  The  greater  reductions  are 
noted  in  the  medium,  the  slighter  decreases  in  the  most  marked  grades  of 
obesity.  If  auxiliary  measures,  such  as  systematic  muscular  exercise,  hydro- 
therapeutie  agents,  mineral  spring  cures,  etc.,  are  utilized,  the  loss  in  weight 
may  readily  be  increased  to  22  to  33  pounds  in  a  month. 

The  following  table  showing  the  success  which  Dapper  attained  in  his 
sanatorium  at  Kissingen,  in  which  the  diet  scheme  was  based  upon  that  pro- 
posed by  me,  is  instructive : 


Number. 

Men. 

Women. 

Weight  at 

the  onset 
in  kilograms. 

Duration  of 

the  treatment 

in  weeks. 

Loss  of  weight 
during  the 

time  in 
kilograms. 

1      

M. 
W. 
M. 
M. 
M. 
W. 
M. 
M. 
W. 
M. 
W. 
M. 
M. 
W. 
M. 
W. 
M. 
M. 
W. 
M. 
M. 
W. 
\Y. 
M. 
M. 

129.5 

104.5 

99.5 

114.5 

104.5 

112.0 

104.5 

111.0 

74.0 

101.0 

97.0 

97.0 

112.0 

107.0 

116.0 

74.7 

96.0 

110.0 

128. 

107.0 

106.7 

113.5 

188.7 

114.0 

105.8 

5 

4* 
2 

4 

5 

5 

3 

41 

5 

5 

4 

2 

4+ 

4 

4 

4 

3i 

4 

4* 

4 

4 

5 

5 

5 

4* 

17  75 

2                     

9  5 

3.                       

4  5 

4 

15  0 

5 

11  5 

6 

10  75 

7                       

5  5 

8 

11 

9                                          

7.5 
10  0 

10 

11 

9  5 

12 

4  5 

18 

10  0 

14.             

9  0 

15         

10  75 

If, 

5  0 

17 

18..             

8.0 
9  5 

19 

10  5 

20 

11  5 

21 

9  5 

22 

10  5 

13  0 

24 

13  5 

25 

10  0 

In  what  proportions  the  main  constituents  of  the  food,  albumin,  f;it.  and 
carbohydrates,  arc  to  be  arranged  in  the  antifal  diel  of  milder  and  medium 
grades  is  of  minor  importance.  The  restriction  of  food  is  not  so  complete 
ilia!  danger  from  uniformity  of  the  diet  is  to  he  feared.  On  the  other  hand. 
the  question  as  to  how  we  are  to  ad  in  antifal  cures  of  the  third  degree  has 
been  much  discussed.  It  cannot  he  considered  of  vital  importance,  for  prac- 
tical experience  has  sufficiently  demonstrated  that  with  a  high  intake  of  albu- 
min (Banting,  Oertel,  Kisch,  v.  Noorden)  as  well  as  with  a  low  intake  of 
albumin  (Ebstein,  Hirschfeld)  satisfactory  results  have  been  attained.  The 
investigations  in  metabolism  of  the  [asl  few  years  an1  in  accord  with  this. 
I  regard   the  question  as  one  of  technic  rather  than  of  theory  or  principle. 


74  OVER-NUTRITION  AND  UNDER-NUTRITION 

Experience  appears  to  prove  that  in  numerous  patients  the  administration 
of  large  amounts  of  meat — equivalent  to  a  high  intake  of  albumin — is  much 
better  than  small  ones.  Meat  is  not  only  the  most  important  food  for  most 
persons,  but  also  the  one  most  desired.  Nevertheless,  there  are  many  corpulent 
persons,  especially  women,  who  dislike  large  amounts  of  meat,  and  in  whom 
any  antifat  diet  that  consists  largely  of  meat  will  certainly  suffer  shipwreck. 
Nothing  can  be  more  unwise  than,  for  the  sake  of  theory,  to  force  the  admin- 
istration of  albumin  up  to  a  certain  height ;  the  requirements  of  the  individual 
case  and  nothing  else  should  be  considered.  But  we  must  insist  on  not  less 
than  the  minimum  of  about  100  grams  of  albumin.  Above  this,  theoretically, 
the  limit  cannot  be  definite.  In  practice,  about  180  grams  of  albumin  per 
day  should  rarely  be  exceeded. 

No  less  warm  than  the  question  of  the  administration  of  albumin  is  the 
discussion,  whether,  among  the  substances  free  from  nitrogen,  more  fat  or 
more  carbohydrate  should  be  given.  The  important  point  is,  that  the  total 
of  these,  according  to  their  calory  values,  must  be  diminished  so  that  the 
total  amount  of  food  reaches  the  degree  aimed  at  in  the  antifat  diet.  But 
both  the  fat  and  the  carbohydrates  must  be  reduced  below  the  average  amount 
if  the  administration  of  nourishment  is  to  be  limited  to  two-fifths  or  three- 
fifths  of  the  average  requirement  (see  above).  If  only  the  one  or  the  other 
is  forbidden  or  limited — whether  it  be  the  fats  or  the  carbohydrates — sufficient 
of  the  other  remains  in  the  diet  to  render  the  result  dubious.  Whether  in 
the  simultaneous  limitation  a  little  more  fat  (Ebstein,  Hirschfeld)  or  a 
little  more  carbohydrate  (Banting,  Oertel,  Kisch,  v.  Noorden)  remains  is  of 
subordinate  importance.  Only  the  calory  total  of  both,  not  the  chemical 
constitution — whether  fat  or  carbohydrates — is  of  significance.  I  regard  it  as 
only  a  question  of  technic  how  far  the  limitation  of  one  or  of  the  other  is  to  be 
carried.  The  wishes,  the  manner  of  life,  and  the  peculiarities  of  the  patients, 
not  the  principles  of  treatment,  are  the  determining  factors.  But  from  my 
own  experience  I  should  like  to  emphasize  the  fact  that,  as  a  rule,  we  attain 
better  results  if  the  fats  are  limited  as  much  as  possible,  and  somewhat  more 
of  carbohydrates  are  permitted  in  the  food;  for  the  carbohydrates  furnish 
a  larger  volume,  satisfy  more  readily,  and  permit  a  much  greater  variation 
in  the  diet. 

Alcohol,  of  course,  must  not  be  given  with  a  free  hand  in  antifat  cures. 
As  already  remarked,  it  saves  fat  and  in  this  manner  favors  its  accumulation. 
Many  persons  owe  their  excessive  adipose  tissue,  primarily,  to  the  immoderate 
use  of  alcohol.  Nevertheless,  almost  all  authors  have  ascribed  to  alcohol  a 
subordinate  place  in  antifat  cures — and  quite  properly  so,  since  in  practice 
its  stimulating  effect  cannot  always  be  dispensed  with.  But  where  it  is  possi- 
ble— particularly  in  young,  robust  people — it  is  wise  to  exclude  alcohol  on 
account  of  its  high  calory  value. 

In  antifat  cures  the  question  of  the  allowance  of  water  is  usually  discussed. 
Among  laymen,  and  also  among  physicians,  the  opinion  prevails  that  the 
intake  of  fluids  favors  the  accumulation  of  fat.  This  is  unquestionably  incor- 
rect. How  easy  and  cheap  would  it  be  for  the  farmer  if  the  administration 
of  water  favored  fattening!     On  the  other  hand,  the  statement  that  antifat 


THE  TECHNIC  OF   OVER-NUTRITION  AND  UNDER-NUTRITION        75 

treatment  is  favored  by  limiting  the  amount  of  water  cannot  be  pronounced 
unqualifiedly  incorrect.  We  must  be  quite  clear  that  this  fact  has  no  bearing 
on  the  relation  between  the  administration  of  water  and  decomposition  of 
fat — as  taught  by  Oertel  and  Schweninger — but  that  water  has  its  effect  by 
influencing  the  intake  of  food.  Many  persons  eat  decidedly  less  when  forbid- 
den to  take  as  much  fluid  as  they  have  been  accustomed  to  doing.  They  cer- 
tainly eat  less  if  the  simultaneous  ingestion  of  fluid  and  solid  food  is  for- 
bidden. The  Lessened  ingestion  of  food  will  then  promote  the  disappearance 
of  body  fat.  But  this  result  cannot  always  be  counted  upon,  for  among  the 
obese  we  meet  many  whose  appetite  is  not  influenced  in  the  least  by  limiting 
the  intake  of  fluid.  They  naturally  remain  fat.  or  even  deposit  more  fat,  no 
matter  how  much  they  are  tormented  by  the  thirst  cure. 

I  have  formulated  the  present  status  of  the  question  in  the  following  state- 
ments : l 

1.  A  limitation  of  the  intake  of  fluid,  according  to  Oertel  and  Schwen- 
inger, has  not  the  slightest  influence  upon  the  decrease  of  body  fat  or  upon 
the  increase  of  fat  metabolism. 

2.  The  primary  effect  of  limitation  of  fluid  upon  body-weight  depends 
upon  the  losses  of  water  from  the  blood  and  the  tissues.  This  may  be  utilized 
therapeutically: 

(a)  To  improve  the  circulatory  conditions  in  endangered  failure  of  the 
heart  (in  cases  of  valvular  disease,  disease  of  the  heart  muscle,  arteriosclero- 
sis, contracted  kidney)  ; 

(l>)  In  patients  with  a  tendency  to  immoderate  production  of  sweat,  and 
for  the  purpose  of  combating  hydrorrhea  : 

(c)  In  some  patients  it  is  a  valuable  auxiliary  remedy  through  suggestion. 

3.  The  influence  of  the  limitation  of  water  upon  fat  metabolism,  particu- 
larly in  decreasing  the  amount  of  fat,  is  only  indirect,  and  comes  into  ques- 
tion only  under  special  conditions,  namely  : 

(a)  If,  by  decreasing  the  fluid  intake,  the  circulatory  disturbances  pres- 
ent are  to  be  compensated;  there  may  he  then  a  possibility  of  favoring  the 
combustion  of  fat  by  muscular. exercise. 

(b)  When,  by  decreasing  the  fluid  intake,  the  appetite  of  the  person  for 

fat-producing  foods  is  diminished.  This  resull  may  appear  in  a  marked 
degree,  more  frequently  in  Blighter  degree,  or  not  at  all. 

4.  When  no  special  indications  are  presenl  the  intake  of  water  i-  not  to 

be   limited    in    the   obese,   as.   without    this,   we   attain    the    same   end    and    the 

limitation  of  water  in  such  cases  is  only  an  unnecessary  hardship  for  the 
patient. 

That,  in  antifat  cures,  liiidcr-nut  lit  ion  is  not  the  only  a-vnf  to  he  em- 
ployed, but  that  this  is  to  In-  assisted  h\  systematic  muscular  exercise,  ha-  been 
reiterated.     I  shall  not  enter  into  individual  point-,  bul   will  only  refer  to 

other  chapters  of  this  hook  in  which  the  treatment  of  obesity  has  Keen  explic- 
itly described. 

Here    it     i-    only    accessary    to    indicate    the    important    point-    that    should 


1  Therapie  <l<  r  Gegenwart,  April,  1900. 


76  OVER-NUTRITION  AND  UNDER-NUTRITION 

be  remembered  in  all  curative  methods  in  which  over-nutrition  and  under- 
nutrition come  into  play.  The  better  the  physician  understands  the  general 
laws  of  these  cures,  the  more  readily  will  he  be  able  to  meet  the  indications 
of  the  individual  case.  The  successes  of  dietetic  therapy  may  only  too  readily 
become  matters  of  routine.  Many  practitioners  adhere  too  closely  to  definite 
diet  schemes  which  have  been  proposed  by  this  or  that  celebrated  author,  or 
they  even  hand  to  the  patients  a  so-called  diet  list  which  refers  only  to  the 
disease,  and  not  to  the  patient,  and  which  means  the  annihilation  of  indi- 
vidual dietetic  therapy.  Only  the  intimate  union  of  practical  experience  with 
a  comprehensive  understanding  of  fundamental  theoretic  laws  will  enable  the 
physician  to  choose  rightly  in  every  case.  He  must  always  bear  in  mind  that, 
although  there  are  many  methods  of  securing  over-nutrition  and  under- 
nutrition, for  the  special  case  there  is  but  one  best  method. 


DIABETES    MELLITUS 

By  13.   NAUNYN,   Strassburg 

Contexts:   I.   Glycosuria  and  Diabetes.     II.  The   Various  Forms  of  Dia- 
betes;  Predisposition.    III.  Mild  and  Severe  Forms  of  Diabetes;  Course, 
Symptoms  and  Complications.     IV.  Theory  and  Treatment.     V.   Prac- 
tical Management.     VI.   Tables;  Diet  Lists;  Scheme  of  Food    Va 
Dietetic  Rules  for  Diabetics. 

I.    GLYCOSURIA   AND    DIABETES 

Glycosuria,  Levulosuria,  Lactosuria  ami  Pentosuria.  Physiologic  and  Alimentary 
Glycosuria.  Alimentary  Glycosuria  e  saccharo;  Non-Diabetic  and  Diabetic  Forms. 
Spontaneous  Non-Diabetic  Glycosurias. 

I',v  the  term  "glycosuria"  we  mean  the  appearance  in  tin-  urine  of  true 
grape-sugar  (dextrose,  glucose),  which  is  dextrorotary.  We  also  speak  of 
"levulosuria/'  when  we  mean  the  excretion  of  Levulose,  a  fruit  sugar  which 
is  levorotary.  "Lactosuria"  means  the  excretion  of  milk-sugar  (lactose). 
A  sugar  containing  five  atoms  of  carbon,  in  its  molecular  composition  known 
a-  pentose,  may  also  appear,  hence  the  term  "  pentosuria." 

Lactosuria  may  occur  during  pregnancy  and  in  nurslings,  and  has  nothing 
in  common  with  diabetes.  Pentose  maj  be  found  in  the  orine  after  the  inges- 
tion of  cherries,  plums  and  beer,  and  occasionally  also  in  diabetic  urine,  hut 
it-  role  in  diabetes  i-  quite  obscure. 

On  the  other  hand,  there  are  cases  <>f  diabetes  mellitus  in  which  levu- 
losuria takes  the  place  of  dextrosuria  and  Levulose  plays  the  pari  in  the 
disease  which  ordinarily  i-  assumed  by  dextrose.  Such  cases  are.  however, 
very  rare,  not   more  than  half  a  dozen  being  known. 

Glycosuria  (dextrosuria)  i-  the  cardinal  symptom  of  diabetes  mellitus, 
hm  ao\  every  case  of  glycosuria  w  "''  ;1  diabetic  nature.  There  i-  a  so-called 
physiologic  glycosuria;  in  other  words,  a  normal  individual  may  excrete  dex- 
trose  in  his  urine,  hut  the  quantity  Is  always  extremely  small.  Disregarding 
for  the  preseni  so-called  alimentary  glycosuria,  the  percentage  of  ~ULrar  in  the 
urine  of  healthy  individuals  is  seldom  more  than  0.05  per  cent.,  although  it 
may  reach  0.1  percent,  or  even  0.2  per  cent. 

It    i-   fortunate  that    the  amount   of  BUgar   in   normal   urine  docs  not    read 

to  the  ordinary  tests.    Trommer's  (or  Fehling's)  and  also  Fischer's  tesl  only 

Lri\e  ,i   positive  reaction   in   urine  when   the  amount   of  -ULrar  present    is  ahnor- 

:: 


78  DIABETES  MELLITUS 

mally  high;  i.e.,  over  0.1  per  cent.,  and  only  when  this  quantity  of  sugar  is 
present  can  it  he  quantitatively  estimated.  If  on  hoiling  urine  in  an  alkaline 
solution  of  copper  sulphate  (Trommers  test)  we  immediately,  not  subse- 
quently, obtain  a  red  or  reddish-yellow  precipitate,  or  if  on  warming  the 
urine  with  Phenylhydrazin  and  acetic  acid  on  a  water-bath  for  half  an  hour, 
a  distinct  crystalline  sediment  is  deposited,  we  may  lie  sure  that  the  glycosuria 
is  not  physiologic.  As  possible  sources  of  error  there  may  be  mentioned  the 
presence  in  the  urine  of  lactose,  pentose,  and  combinations  of  glycuronic 
acid  (after  the  administration  of  chloral,  chloralamid,  etc.).  Lactose  and 
pentose  as  well  as  combinations  of  glycuronic  acid  have  a  considerable  power 
of  reduction,  but  we  may  readily  distinguish  them  from  dextrose  by  the 
fermentation  test  and  by  polarization. 

In  diabetes,  then,  we  are  concerned  only  with  hyperglycosuria,  or,  in 
other  words,  with  cases  in  which  the  sugar  exists  in  such  quantities  as  to 
react  readily  to  the  above  mentioned  tests.  But  hyperglycosuria  may  exist 
independently  of  diabetes.  The  so-called  alimentary  glycosuria  is  a  case  in 
point :  a  person  whose  urine  does  not  contain  sugar  partakes  of  sugar  or 
sugar  forming  substances  (starchy  material,  dextrin)  in  sweetened  foods  and 
liquids,  beer,  bread  or  potatoes,  etc. ;  if  sugar  then  appears  in  the  urine  so 
that  it  may  be  detected  by  means  of  any  of  the  ordinary  quantitative  tests, 
this  condition  is  designated  alimentary  glycosuria. 

In  diabetics  whose  urine  is  temporarily  free  from  sugar,  this  is  of  quite 
regular  occurrence.  It  also  takes  place  in  non-diabetics,  but  with  this  differ- 
ence, that  in  the  diabetic  the  sugar  producers  in  the  food — the  flour  in  bread, 
etc. — if  consumed  in  large  amounts  give  rise  to  glycosuria  almost  as  surely 
as  the  sugar  itself,  while  this  condition  only  occurs  in  the  non-diabetic  from 
sugar  and  not  from  starchy  substances. 

Therefore,  glycosuria  after  the  ingestion  of  sugar  need  not  be  diabetic, 
but  may  be  produced  in  normal  persons  even  up  to  several  per  cent.,  provided 
the  sugar  .  (grape-sugar,  milk-sugar,  or  cane-sugar)  is  given  upon  an  empty 
stomach  in  amounts  of  100  grams  and  over.  If  such  a  glycosuria  occur  after 
the  consumption  of  100  grams  of  sugar  (usually  grape-sugar  is  used)  when 
the  stomach  is  no  longer  empty,  we  are  dealing  with  abnormal  glycosuria, 
i.  e.,  alimentary  glycosuria  e  saccharo.  This  may  indicate  diabetes  or  be  the 
first  sign  of  the  development  of  the  disease;  in  other  words,  the  person  in 
question  may  develop  diabetes  sooner  or  later,  but  not  necessarily;  the  indi- 
vidual need  not  be  a  diabetic,  nor  even  become  one. 

Taking  as  a  criterion  the  nature  of  the  processes  concerned,  let  us  now 
attempt  to  differentiate  between  diabetic  and  non-diabetic  glycosuria. 

In  the  diabetic,  the  organs  which  are  concerned  in  the  consumption  of 
sugar  have  suffered  damage  and  are  incapacitated  for  work ;  they  fail  to  extract 
the  sugar  from  the  blood  which  is  brought  to  them,  or  they  return  it  to  the 
circulation,  as  they  are  incapable  of  utilizing  it.  Thus  a  hyperglycemia  and 
consequent  glycosuria  arises,  provided  the  amount  of  sugar  in  the  blood  is 
more  than  0.2  per  cent-0,3  per  cent.,  and  this  is  a  diabetic  hyperglycemia 
and  glycosuria.  The  condition  depends  upon  obstruction  to  the  normal  drain- 
age of  sugar  from  the  blood  by  the  organs  of  sugar  metabolism,  and  it  is  for 


GLYCOSURIA  AND   DIABETES  79 

this  reason  that  sugar  is  excreted  by  the  kidneys.  But  the  organs  whose 
function  it  is  to  burn  sugar  cannot  take  up  from  the  blood  and  consume  an 
unlimited  amount  of  sugar,  even  if  they  and  all  the  other  organs  are  per- 
fectly sound  and  function  normally.  It  is  true  that  a  flooding  of  the  blood 
with  sugar  can  hardly  occur  in  health  through  the  ingestion  of  starches,  even 
in  the  largest  amounts,  as  these  are  absorbed  too  slowly,  but  it  may  readily 
occur  after  ingestion  of  large  quantities  of  readily  absorbable  sugar  solu- 
tions. That  alimentary  glycosuria  (e  saccharo)  may  be  explained  in  this 
manner  is  evident  from  the  fact  that  in  most  of  these  cases  tin1  sugar 
(for  example,  milk-sugar  or  levulose)  is  excreted  in  the  same  form  in  which 
it  is  introduced.  This  explanation  is  also  favored  by  the  circumstance  that 
alimentary  glycosuria  occurs  more  readily  when  the  stomach  is  empty,  for,  as 
is  well  known,  absorption  is  then  more  rapid.  This  pathologic  but  non- 
diabetic  alimentary  glycosuria  (e  saccharo)  is  probably  due,  therefore,  to  an 
abnormally  hastened  absorption  of  the  sugar  solution. 

Finally,  non-diabetic  glycosuria,  i.e.,  glycosuria  despite  a  normal  condi- 
tion of  the  sugar-consuming  organs,  may  occur  when  the  renal  secretion  has 
become  so  increased  that  sugar  and  other  solids  are  drawn  out  of  the 
blood  in  abnormally  large  quantities  and  excreted  with  the  urine.  Perhaps 
it  may  be  possible  to  explain  in  this  way  the  fact  that,  after  the  ingestion  of 
much  beer  or  champagne,  sugar  (even  several  per  cent.)  is  occasionally  found 
in  the  urine. 

It  is  possible,  however,  that  in  these  "beer  glycosurias'"  the  damaging 
influence  of  the  alcoholic  beverage  upon  the  liver  is  also  a  factor;  the  possi- 
bility is  obvious  enough,  since,  in  cirrhosis  of  the  liver,  alimentary  glycosuria 
ia  frequent.  In  these  cases  we  are  then  concerned  with  diabetic  glycosuria, 
i.e.,  with  the  complication  of  cirrhosis  of  the  liver  and  diabetes  mellitus. 

This  example  shows  how  difficulf  it  is  to  separate  alimentary  glycosuria 
from  the  diabetic  form,  and  there  are  many  other  illustrations  of  this  diffi- 
culty. Thus,  in  traumatic  neuroses  true  diabetes  may  occur.  On  the  other 
hand,  alimentary  glycosuria  (e  saccharo)  is  a  particularly  frequenl  symptom 
in  traumatic  neuroses.  And  one  cannot  look  upon  this  sign,  in  all  cases, 
as  indicating  diabeti — at  any  rate  in  the  overwhelming  majority  of  cases 
Buch  a  condition  does  not  arise.  In  exophthalmic  goiter  the  same  state  of 
affairs  exists.  Taken  all  in  all.  in  every  alimentary  glycosuria,  including  the 
"e  saccharo  "  variety,  it  is  Qecessary  to  observe  great  caution  in  deciding 
whether  this  is  a  sign  of  diabetes  or  not.  Alimentary  glycosuria  following 
the  ingestion  of  Btarch  musl  always  be  looked  upon  as  a  sign  of  true  diabetes. 

" Experimental "  glycosuria  in  the  human  Nein--  does  not  play  a  greai 
role,  although  it  occasionally  occur — for  example,  glycosuria  after  poison- 
ing with  coal  gas.  or  with  phloridzin  for  purposes  of  malingering.  These 
conditions  musl  be  understood  in  order  to  recognize  thai  they  are  noi  cases 
of  diabetes. 

In  all  cases  of  spontaneous  glycosuria  (non-alimentary)  the  greatest  care 
is  necessary  before  deciding  whether  they  are  to  be  Looked  upon  as  Bign 
diabetes  or  not.    We  musl  he  -ure  ihai  pentose  or  glycuronic  acid  in  the  urine 
is  not   mistaken   for  glycosuria;  when  lactosuria  occurs  in  pregnancy  or  in 


80  DIABETES  MELLITUS 

the  puerperal  state,  we  must  know  that  this  has  nothing  to  do  with  diabetes. 
As  an  example  of  true  glycosuria  appearing  spontaneously  in  man,  yet  not 
the  expression  of  diabetes,  I  can  only  mention  the  form  occurring  in  cholera 
asiatica  and  cholera  nostras. 

All  other  forms  (unless  proofs  are  present  to  the  contrary)  should  be 
looked  upon  as  diabetic ;  but  we  need  to  know  what  is  meant  by  diabetes,  i.  e., 
the  disease  of  this  name  as  it  occurs  in  the  human  subject. 


II.   THE    VARIOUS    FORMS    OF    DIABETES; 
DIABETIC    PREDISPOSITION 

Acute  Diabetes,  the  Acute  Form  Terminating  Fatally  and  the  Acute  Form  Resulting 
in  Recovery — Transitory,  Nervous  (Cerebral  Trauma),  and  Pancreatic  Glycosuria 
Representing  the  Shortest  Course  of  Acute  Diabetes  Mellitus  Terminating  in  Recovery. 
Chronic  Diabetes  Mellitus  as  an  Expression  of  an  Hereditary  Predisposition.  Its 
Three  Varieties:  (a)  The  Pure  Form,  (b)  Diabetes  of  the  Aged,  and  (c)  Organic 
Diabetes  Mellitus.  Etiology  of  Diabetes  Mellitus  and  the  Possibility  of  its  Cure  in 
the  Light  of  Hereditary  Predisposition — the  Heredity  of  Diabetes  Mellitus.  One  Form 
or  Several  Forms  of  Diabetes? 

Diabetes  is  generally  considered  a  chronic  affection,  but  it  may  take  an 
acute  course  and  be  either  rapidly  fatal  or  readily  curable. 

"Well  studied  cases  with  an  acutely  fatal  course  have  been  reported;  for 
instance,  Wallach  reports  the  case  of  a  chemist  who  was  accustomed  to  make 
weekly  examinations  of  his  own  urine.  The  urine  was  always  free  from  sugar 
until  suddenly  a  severe  glycosuria  appeared,  and  within  five  weeks  the  man 
died  in  diabetic  coma. 

The  question  of  acute  cases  that  terminate  in  recovery  is  less  simple. 

Schmitz  reports  the  case  of  a  four-year-old  child  of  a  diabetic  mother. 
The  anxious  mother  had  the  urine  of  the  child  examined  frequently,  and  it 
was  always  free  from  sugar  up  to  November  22,  1871.  On  November  26th, 
the  child  was  attacked  by  a  gastric  fever,  and  on  the  27th  the  sugar  contained 
in  the  urine  amounted  to  5.8  per  cent.  The  child  was  put  upon  strict  diet, 
and  on  the  13th  of  December  the  urine  was  again  free  from  sugar.  Although 
the  patient  gradually  returned  to  the  usual  saccharine  and  amylaceous  diet 
the  urine  remained  normal  for  twenty  years.  Whether  it  is  correct  to  say 
that  the  diabetes  had  already  been  cured  upon  the  13th  of  December  is  at 
least  very  questionable,  for  at  that  time,  and  for  a  long  period  afterward,  the 
child  lived  upon  a  very  strict  diet,  which  later  was  even  more  restricted,  so 
that  very  little  was  expected  from  its  carbohydrate  metabolism.  On  Decem- 
ber 13th,  the  recovery  was  probably  only  relative. 

Zinn  observed  a  child  attacked  by  diabetes  mellitus  after  scarlatina ;  the 
patient,  after  ten  weeks,  even  upon  "mixed  diet"  showed  no  sugar  in  the 
urine;  unfortunately  the  observations  in  regard  to  the  recovery  were  only 
continued  for  a  few  months. 

Similar  conditions  may  be  observed  in  all  cases  of  true  diabetes  in  which 
recovery  takes  place. 

Diabetes  after  cerebral  injuries  also  occurs  as  an  acute  disease  which  may 


THE  VARIOUS   FORMS   OF  DIABETES  81 

terminate  in  recovery.  As  a  result  of  trauma  of  the  brain  we  note  eases  of 
diabetes  that  are  severe,  even  very  severe;  then  there  are  eases  which  run  a 
milder  course  similar  to  those  of  Schmitz  and  Zinn  mentioned  above;  finally, 
there  are  cases  after  cerebral  injuries,  in  which  transitory  glycosuria,  without 
any  further  consequences,  occurs  and  lasts  but  a  few  days.  What  right  have  we 
to  deny  that  these  transitory  glycosurias  represent  the  mildest  forms  of  dia- 
betes mellitus?  The  same  lessons  which  are  taught  us  by  the  study  of  diabetes 
after  cerebral  injury  in  the  human  subject  are  paralleled  as  regards  pancreatic 
diabetes  by  experiments  upon  animals;  extirpation  of  the  pancreas  produces 
the  most  -evere  forms  of  chronic  diabetes;  transitory  lesions  of  the  organ 
produce  mild  ephemeral  glycosuria. 

In  my  opinion  we  must  admit  that  diabetes  may  occur  as  an  acute  affec- 
tion, and  this  conclusion  has  some  practical  importanee ;  spontaneous,  true, 
acute  diabetes  is  certainly  very  rare,  but  transitory,  spontaneous  (?)  gly- 
cosuria may  be  explained  in  this  manner: 

Although  the  course  of  the  disease  is  for  the  most  part  ehronic.  the  con- 
ditions are  not  accurately  designated  if  we  call  diabetes  "a  chronic  disease"; 
in  the  majority  of  cases  there  is  an  innate  hereditary  predisposition,  a  weak- 
aess  of  sugar  metabolism,  which,  sooner  or  later,  in  combination  with  other 
causes,  or  even  without  such,  may  lead  to  insufficiency  of  sugar  metabolism 
and  thus  give  rise  to  the  disease. 

According  to  this,  three  forms  of  the  disease  may  be  differentiated: 

1.  Diabetes  mellitus  of  young  individuals  (those  between  thirty  and  forty 
years  of  age)    ("pure  diabetes"). 

In  this  form  the  hereditary  weakness  of  sugar  metabolism,  without  the 
association  of  any  special  disease  of  an  organ,  progresses  to  Insufficiency. 
This  occurs  at  an  early  period  of  life,  owing  to  a  particular  severity  of  the 
pathologic  predisposition,  and,  in  keeping  with  this,  the  eases  are  for  the  most 
part  serious. 

2.  Diabetes  of  Hir  aged,  the  usual  mild  diabetes  of  old  persons;  the  saying 
that  "the  age  of  an  individual  depends  upon  the  condition  of  his  arteri 

i-  also  true  in  these  cases;  usually,  arteriosclerosis  is  the  underlying  condi- 
tion and  with  this  all  factor-  are  operative  which  favor  it<  development;  lux- 
urious living  and.  above  all.  the  use  of  alcohol. 

Tt  is  readily  seen  that  the  leasl  severely  predisposed  cases  are  the  ones  in 
which  thi-  form  of  diabetes  is  mosl  likely  to  appear:  perhaps  this  accounts 
for  its  relatively  mild  course. 

3.  Organic  diabetes;  tin-  refers  to  cases  in  which  disease  of  a  particular 
organ  is  the  immediate  cause  of  the  affection.  A-  example-,  there  may  he 
mentioned:   (a)  anion--  the  diseases  of  the  liver,  cirrhosis  and.  rarely,  chronic 

cholelithiasis;  (M  anion--  diseases  of  the  uervous  Bystem,  apoplexy,  chronic 
encephalomalacia,  cerebral  syphilis,  dementia  paralytica,  tabes  dorsalis,  i 

bra!  trauma  of  all  kind-,  the  variou-  functional  ueurose8,  particularly  the  trau- 
matic ones,  and  paralv-i-  agitans;  (c)  diseases  of  the  thyreoid  -land  (Graves' 
disease),  and  (>!)  diseases  of  the  pancreas. 

Experimental  evidence  would  Beem  to  show  that  the  pancreas  fake-  the 
tir-t  position  among  the  organs  which  cause  diabetes,  since  by  extirpation  or 
7 


82  DIABETES  MELLITUS 

by  a  more  or  less  extensive  resection,  true  diabetes  may  be  produced.  Our 
investigations  in  man,  however,  only  correspond  with  this  in  so  far  as  extir- 
pation of  the  pancreas  and  disease  of  the  pancreas  also  cause  diabetes  in  the 
human  subject.  On  the  other  hand,  diseases  of  the  pancreas  have  only  in 
rare  instances  been  determined  with  certainty  as  the  cause  of  diabetes;  these 
affections  are  pancreatic  calculi,  pancreatic  cirrhosis,  neoplasms  and  cysts. 

If  we  have  disease  in  an  organ  which  is  very  influential  in  sugar  metabo- 
lism, as,  for  instance,  the  nervous  system  or  pancreas,  this  suffices  to  produce 
diabetes,  even  without  a  previous  predisposition;  if,  however,  a  predisposi- 
tion exists,  disease  of  one  of  the  vital  organs  is  not  absolutely  necessary. 
Slight  general  disturbances  are  sufficient  to  bring  about  an  insufficiency  in 
sugar  metabolism.  Thus  the  varying  etiology  of  diabetes  mellitus  becomes 
comprehensible,  and  we  learn  to  recognize  as  causes  not  only  the  above  men- 
tioned organic  diseases,  but  also  many  severe  or  mild  general  affections : 
influenza,  enteric  fever,  scarlatina,  erysipelas,  phlegmons,  syphilis,  and, 
finally,  the  most  manifold  forms  of  trauma,  surgical  operations,  psychical  dis- 
turbances, bodily  or  mental  over-exertion,  indigestion  and  excesses  of  all 
kinds;  all  of  these  are  occasionally  of  etiological  significance  in  diabetes 
mellitus. 

This  conception  of  diabetes  mellitus  as  an  expression  of  an  hereditary 
weakness  of  metabolism  makes  clear  at  once  what  we  can  expect  as  regards 
the  cure  of  diabetes. 

One  can  speak  of  actual  cure  only  in  those  cases  in  which  the  disease 
appears  as  the  result  of  an  affection  of  one  of  the  principal  organs;  if  an 
affection  of  the  organs  in  question  improves,  then  diabetes  may  actually  be 
"cured."  That  this  occurs  is  certain  (in  man)  in  the  case  of  diabetes  as  the 
result  of  brain  injuries. 

If,  however,  as  in  most  cases,  the  cause  of  diabetes  must  be  referred  to 
hereditary  predisposition,  we  must  at  once  assume  a  skeptical  attitude  in 
regard  to  the  cure,  all  the  more  so  if  the  predisposition  is  the  only  causal 
factor.  Where  other  causes  are  associated  with  this,  e.  g.,  cirrhosis  of  the  liver, 
infectious  diseases,  especially  syphilis  (we  may  remark  in  passing  that  syphi- 
lis plays  but  a  very  slight  role  in  the  etiology  of  diabetes),  arterio-sclerotic 
circulatory  disturbances,  we  have  more  reason  to  hope  that,  by  treatment  or 
by  cure  of  the  causes  simultaneously  present,  sugar  metabolism  may  again 
become  sufficient,  but  the  predisposition  remains,  and  with  it  the  danger  that 
any  fresh  damage  may  bring  about  a  relapse. 

Many  cases  may  be  explained  in  this  way;  for  example,  an  elderly  person  who  may 
have  suffered  many  years  ago  with  diabetes,  is  apparently  cured;  i.  e..  he  returns  to  his 
usual  mode  of  living  without  paying  much  attention  to  his  "  cured  "  diabetes.  The 
urine  is  free  from  sugar;  he  is  then  attacked  with  influenza,  or  undergoes  some  marked 
psychical  disturbance,  and  the  glycosuria  at  once  returns  quite  severely ;  or  he  has  to 
submit  to  an  operation,  and  after  the  operation  a  coma  ensues,  coma  diabeticum,  the 
urine  containing  many  per  cent,  of  sugar. 

We  are  justified  in  assuming  (as  we  have)  an  hereditary  predisposition 
for  many  cases  of  diabetes,  apart  from  what  has  already  been  said,  by  the  fact 
of  the  heredity  of  the  disease.    In  most  cases  of  diabetes,  heredity  is  a  factor ; 


MILD  AND  SEVERE  FORMS  OF  DIABETES  83 

it  has  been  proven  in  more  than  30  per  cent,  of  my  eases,  and  becomes  more 
frequent  the  more  closely  I  investigate.  This  hereditary  predisposition  is 
true  of  all  three  varieties,  and  can  be  demonstrated  in  a  like  number  of  cases 
of  the  organic  form,  in  diabetes  of  the  aged,  and  in  "  pure  diabetes."  The 
hereditary  factor  in  diabetes  is  related  to  the  neuropathic  taint  and  to  the  pre- 
disposition to  gout  and  obesity.  In  many  families  gout  or  some  variety  of 
neurosis  or  psychosis  occurs  alternately  with  diabetes,  and  if.  in  such  diabetic 
families,  one  of  the  members  is  conspicuously  fat.  this  is  very  suspicious  of 
diabetes.  These  are,  incidentally,  the  cases  for  which  the  improperly  used 
term  "  diabetes  of  the  obese  "  should  be  reserved,  the  cases,  namely,  in  which 
obesity  points  to  diabetes. 

It  is  often  said  that  as  the  cases  of  diabetes  are  quite  different,  and  as  these 
etiologic  differences  correspond  with  differences  in  the  course  and  the  symp- 
tomatology, diabetes  should  no  longer  be  looked  upon  as  a  single  disease.  We 
should  no  longer  speak  of  "diabetes  mellitus,"  but  of  "various  forms"  of 
diabetes  mellitus.  But  in  answer  to  this  we  must  again  emphasize  in  all 
forms  of  diabetes  the  hereditary  predisposition.  This  is  the  common  bond 
which  holds  these  various  forms  together;  it  is  operative  in  each  of  the 
varieties  which  are  to  be  differentiated  etiologically.  In  every  type  of  the 
disease,  in  nervous  diabetes,  as  well  as  in  liver  diabetes,  in  diabetes  after 
infections,  in  diabetes  of  the  aged,  and  in  "pure"  diabetes,  30  per  cent,  (or 
more)  are  hereditary  cases. 

Further,  we  do  not  know  at  present  whether  the  pathogene-i»  <>\'  glycosuria, 
i.  e.,  the  disturbance  in  metabolism  which  causes  it  in  the  different  cases,  is 
as  multiform  as  the  etiology;  on  the  contrary,  the  glycosuria  which  occurs  in 
all  the  various  types  of  diabetes  mellitus  (so  far  as  This  point  has  1 n  inves- 
tigated) is  hyperglycemic  in  origin,  i.e..  the  condition  is  due  to  an  increase 
in  the  amount  of  sugar  in  the  blood.  This  is  only  true,  however,  of  diabetes 
mellitus  as  it  occurs  in  man  ;  we  can  produce  in  animals  and  in  man  an  experi- 
mental glycosuria  which  is  not  hyperglycemic,  i.  e.,  the  form  due  to  phloridzin. 
In  animals  even  the  most  marked  phloridzin  glycosuria  produces  no  note- 
worthy increase  of  Bugai  in  the  Mood. 

We  cannot,  therefore,  gee  any  sufficient  reason  for  speaking  of  "  various 
forms"'  of  diabetes,  but  we  do  distinguish  a  mild  and  a  severe  form  of  the 
disease.  This  distinction  will  be  observed  throughout  the  following  descrip- 
tion of  the  symptomatology  and  it  will  also  be  seen  thai  we  have  taken  full 
account  of  the  difference-  in  etiology  between  different  groups  of  diabetic  cases. 

III.    MILD    AND    SEVERE    FORMS    OF    DIABETES;    COURSE, 
SYMPTOMATOLOGY  AND    COMPLICATIONS 

Mild  and  seven-  forms  of  diabetes  mellitus.  The  importance  of  complicating  organic 
disease  in  the  symptomatology  of  the  mild  eases.  Differentiation  of  the  various  sym|>- 
toms  according  to  whether  they  are  due  to  the  organic  disease  or  to  diabetes  mellitus. 
Hyperglycemia  as  a  cause  of  the  hitter.    The  albuminuria  of  the  diabetic 

In  practice  we  cannot  avoid  differentiating  between  mild  and  severe  i 
or  the  mild  and  severe  forms  of  diabetes  mellitus.     It  is  true  that  this  i-  onlv 


84  DIABETES  MELLITUS 

a  difference  of  degree ;  the  nature  of  the  affection  depends  upon  the  same 
process  in  the  mild  and  in  the  severe  cases,  and  transitional  forms  are  by  no 
means  rare. 

Well  developed  cases  of  the  mild  and  of  the  severe  variety  resemble  one 
another  as  little  as  an  epileptic  migraine  resembles  typical  severe  epilepsy, 
or  even  less.  When,  in  a  severe  case  of  diabetes,  4  to  15  or  more  liters  of  urine 
are  passed  with  a  specific  gravity  of  1.025  to  1.040,  or  even  1.060,  and  a  per- 
centage of  sugar  from  5  per  cent,  to  12  per  cent,  daily  (200  to  1,500  grams 
of  sugar  daily),  it  is  obvious  that  there  must  be  an  enormously  increased 
intake  of  nourishment ;  yet  it  is  easy  to  understand  that  in  spite  of  this  the 
patient  emaciates,  becomes  debilitated,  and  soon  perishes.  The  course  of  the 
disease  in  such  cases  is  necessarily  brief.  Often  within  a  few  weeks  the  body- 
weight  falls  to  60  kilograms  in  a  man  or  50  kilograms  in  a  woman,  and  in 
spite  of  all  endeavors  to  prevent  this,  the  patient's  condition  becomes  pro- 
gressively worse;  in  from  one  and  a  half  to  three  years  increasing  cachexia, 
diabetic  coma,  or  pulmonary  tuberculosis,  terminates  life. 

Mild  cases  of  diabetes  may  exist  undiscovered  for  years,  even  decades, 
until  a  complication  or  an  accident  leads  to  the  discovery  of  the  glycosuria; 
so  vague  may  this  condition  be.  In  such  cases  only  10,  30  or  50  grams  of 
sugar  are  excreted  daily,  with  a  normal  or  slightly  increased  amount  of  urine 
in  twenty-four  hours,  and  this  state  of  things  may  go  on  indefinitely,  although 
the  patient  before,  as  well  as  after,  the  discovery  of  the  sugar  pays  but  slight 
attention  to  his  condition.  If  he  limits  the  amount  of  beer,  bread  and  starchy 
food  and  gives  up  sugar  and  potatoes  entirely,  this  will  suffice  to  keep  his 
glycosuria  within  the  limits  above  mentioned,  whereas,  in  a  severe  case,  even 
the  strictest  diet  only  brings  about  an  amelioration,  and  the  patient's  whole 
life  becomes  a  combat  with  glycosuria,  a  battle  for  existence.  If  glycosuria 
is  a  symptom  in  a  mild  case  of  diabetes,  in  a  severe  case  it  is  the  disease,  the 
fatal  disease  itself.  The  loss  of  sugar  in  the  urine,  the  impossibility  of  com- 
pensating for  it  by  an  increased  nourishment,  and  the  consequences,  among 
which  coma  is  common,  are  the  conditions  from  which  the  patient  suffers  and 
to  which  he  finally  succumbs. 

In  the  severe  cases  glycosuria  itself  is,  in  a  certain  sense,  the  main  disease, 
since  usually  in  cases  of  "  pure  "  diabetes  no  disease  of  any  special  organ  can 
be  found.  It  is  not  necessary  to  discuss  the  question  whether  in  these  cases 
of  "  pure  "  diabetes  we  are  justified  in  looking  upon  a  disease  of  some  special 
organ — generally  the  pancreas — as  the  cause  of  the  disturbances  of  metabolism. 
On  account  of  my  own  position  in  regard  to  pancreatic  diabetes  I  have  par- 
ticularly interested  myself  in  this  question ;  but  it  is  impossible  to  prove  in 
these  severe  cases,  either  from  the  symptoms  and  signs  present  during  the 
life  of  the  patient,  or  at  the  autopsy,  anything  which  points  to  disease  of  the 
pancreas  or  of  any  other  organ.  There  are,  as  has  already  been  mentioned, 
cases  of  diabetes  due  to  disease  of  the  pancreas,  pancreatic  calculi,  cirrhosis  of 
the  pancreas,  etc.,  but  they  are  rare. 

The  mild  cases  rarely  belong  to  the  type  classified  as  "pure"  diabetes; 
more  frequently  the  symptoms  point  to  hepatic  diabetes,  to  nervous  diabetes, 
or  to  diabetes  of  the  aged  (arteriosclerotic  diabetes).     Nevertheless,  "pure" 


MILD  AND  SEVERE   FORMS  OF   DIABETES  85 

diabetes  may  occasionally  run  a  mild  course,  and  cases  of  the  other  form  may 
sometimes  be  severe ;  this  latter  course  is  most  frequently  seen  in  the  diabetes 
which  occurs  after  trauma  of  the  brain. 

Xot  infrequently  the  symptoms  of  the  accompanying  disease  (hepatic, 
nervous,  or  arterio-sclerotic)  are  much  more  prominent  than  the  slight  gly- 
cosuria, and  so  it  happens  that  the  cirrhosis,  or  the  tabes,  in  spite  of  the  com- 
plicating diabetes,  runs  the  same  course  which  it  would  have  assumed  without 
the  associated  condition.  In  arterio-sclerotic  diabetes,  as  the  disease  develops, 
the  arterio-sclerosis  may  become  more  and  more  prominent,  presenting  circu- 
latory  disturbances,  cardiac  asthma,  angina  pectoris,  dropsy,  congested  liver 
and  albuminuria  ;  in  all  of  these  cases  we  may  note  that,  as  they  progress, 
tin'  glycosuria  decreases  and  finally  disappears. 

Although  in  many  of  these  cases  the  glycosuria  does  not  become  promi- 
nent, nevertheless,  the  diabetes  and  the  diabetic  disturbances  of  metabolism 
usually  do  not  fail  to  produce  evil  consequences;  on  the  contrary,  there  is 
quite  an  array  of  complications  and  symptoms  which  appear  frequently  in 
mild  cases;  pruritus  pudendorum,  vaginitis,  vulvitis,  balanitis,  phimosis,  ure- 
thritis, impotence,  fermentation  of  the  urine  in  the  bladder  (with  pneuma- 
turia).  and  as  a  consequence  of  this,  cystitis  and  pyelonephritis;  itching  of 
the  -kin.  urticaria,  eczema,  the  most  manifold  ulcerating  dermatoses,  furun- 
culosis,  carbuncle,  lymphangitis,  boils,  intermittent  claudication,  gangrene  of 
the  to.-,  necrosis  of  internal  organs,  pulmonary  gangrene,  pulmonary  tubercu- 
losis; also  a  host  of  nervous  diseases;  encephalomalacia,  column  degeneration 
of  the  spinal  cord,  neuritis,  polyneuritis,  neuralgia,  peripheral  paralyse-  (par- 
ticularly paralysis  of  the  facial  nerve),  malperforant,  very  frequently  loss 
of  the  patella  reflex  which  occasionally  ushers  in  the  remarkable  picture  of 
pseudo-tabes  diabetica. 

It  is  impossible  to  bring  this  confused  array  into  any  systematic  arrange- 
ment  :  any  one  of  these  symptoms,  or  complications,  may  appear  alone  as  the 
firs!  sign  of  a  diabetes,  latent  up  to  them;  each  of  these  conditions  may  remain 
the  only  one.  or  be  succeeded  in  any  order  by  any  of  the  other-. 

For  some  of  these  conditions  diabetes  alone  cannol  be  held  responsible; 
thus  arterio-sclerosis  is  the  true  cause  of  gangrene  of  the  extremities  with  it- 
occasional  prodrome,  claudicatio  intermittens,  perhaps  also  of  malperforant. 
This  is  true,  even  though  these  lesions  occur  during  the  course  of  a  case  of 
diabetes.  In  the  peripheral  paralyses  and  neuralgias,  the  neuropathic  predis- 
position doubtless  often  plays  a  part,  ami  the  diabetics  that  suffer  from  poly- 
neuritis are.  a-   far  a-   I    know,  all   alcoholics. 

Naturally  the  question  next  arises  whether  diabetes  ha-  any  influence  at 
all  in  the  production  of  these  lesions;  for  example,  in  cardiac  asthma  or  in 
angina  pectoris  of  the  diabetic;  take  the  case  of  an  old  diabetic,  with  a 
glycosuria  of  from  •'!  per  cent,  to  i  peT  cent.,  from  '>"  to  60  grams  of  sugar 
per  day,  suffering  from  cardiac  asthma  or  angina  pectoris;  there  is  slight 
venous  stasis  of  the  liver,  occasionally  slighl  albuminuria:  nothing  abnormal 
can  be  detected  in  the  heart.  Nevertheless,  there  i-  a  well-grounded  suspicion 
that  a  beginning  cardiac  insufficiency,  perhaps  due  to  myocardial  degenera- 
tion  and    perhaps    to  arterio-sclerosis,    j<   present.      Removal    of   the  glycosuria 


86  DIABETES  MELLITUS 

helps  but  little;  digitalis,  however,  soon  brings  relief.  We  must  not  be  too 
certain  that,  in  these  complications  of  diabetes,  glycosuria  does  not  play  a 
part,  and  we  should  never  fail  to  attempt  to  remove  the  glycosuria,  for  there 
are  cases,  like  the  one  just  described,  in  which  no  result  can  be  obtained  with- 
out this  method  of  treatment.  It  should  remain  a  rule  that  wherever  there 
is  even  a  possibility  that  the  symptom  present  is  of  a  diabetic  nature,  the 
attempt  must  be  made  to  reduce  the  glycosuria. 

We  are  compelled,  then,  seriously  to  consider  glycosuria  as  the  cause  of 
these  symptoms.  Glycosuria  may  produce  symptoms  in  two  ways:  First,  by 
the  loss  of  sugar;  of  this  we  have  already  spoken  and  shall  have  to  refer  to 
it  again  frequently;  in  mild  diabetes  the  loss  of  sugar  is  not  important,  and 
glycosuria  as  such  is  only  to  be  considered  as  the  cause  of  urinary  fermenta- 
tion and  its  consequences,  such  as  pneumaturia,  cystitis,  pyelonephritis, 
pruritus  pudendorum,  balanitis,  vaginitis,  etc.  In  mild  diabetes  it  is  the 
hyperglycemia  that  we  hold  responsible  for  symptoms. 

As  long  as  the  diabetic  excretes  sugar,  the  sugar  contents  of  his  blood  is 
increased  above  the  normal  and  there  is  hyperglycemia.  In  marked  glycosuria 
(above  1  per  cent.)  the  hyperglycemia  amounts  to  over  0.2  per  cent,  and  in 
the  severe  grades  of  glycosuria  it  may  amount  to  0.7  per  cent. ;  if  the  gly- 
cosuria is  slight  (^  per  cent,  to  1  per  cent.),  or  if  the  urine  of  the  patient 
is  free  from  sugar,  the  hyperglycemia  is  very  slight,  scarcely  amounting  to 
more  than  0.1  per  cent,  (which  is  almost  normal),  and  then  the  condition  is 
not  serious. 

Diabetic  hyperglycemia  may  certainly  be  held  responsible  for  the  loss  of 
resistance  of  the  diabetic — even  of  the  mild  cases — toward  infections ;  at  least 
it  has  been  experimentally  proven  that  many  of  the  pathogenic  microbes  flour- 
ish better  in  the  tissues  which  contain  sugar.  I  shall  include,  besides  this, 
the  cutaneous  atfections  and  the  neuralgias  as  among  the  complications  de- 
pendent upon  the  hyperglycemia,  basing  my  opinion  upon  the  results  of  the 
therapeutic  removal -of  glycosuria.  Eemoval,  perhaps,  implies  too  much;  it 
would  be  more  correct  to  say  reduction,  for  to  render  the  hyperglycemia 
innocuous,  it  is  almost  always  sufficient  to  reduce  the  glycosuria  to  the  limit 
mentioned  above. 

Regarding  the  symptomatology  and  complications  of  diabetes,  I  must  limit 
myself  to  what  has  been  previously  mentioned.  The  other  important  symp- 
toms not  yet  enumerated,  for  instance,  coma,  will  be  spoken  of  elsewhere; 
only  in  regard  to  albuminuria  I  should  like  to  add  a  few  words. 

Albuminuria  has  one  significance  in  mild  and  another  in  severe  cases; 
in  mild  cases,  the  albuminuria  is  the  expression  of  a  renal  affection  inde- 
pendent of  the  diabetes,  although  in  some  cases  arteriosclerosis  or  hepatic 
cirrhosis  may  represent  a  connection  between  these  diseases  and  the  diabetes. 
In  severe  diabetes,  the  albuminuria  may  be  referred  directly  to  the  diabetes ; 
it  is  the  consequence  of  the  excessive  functional  irritation  from  which  the 
kidney  suffers  owing  to  the  continued  polyuria. 

Perhaps  the  abnormal  constitutents  of  diabetic  urine,  possibly  the  sugar 
itself,  may  irritate  the  renal  elements.  But  this  diabetic  albuminuria  is  not 
nephritic  in  origin,  i.  e.,  it  does  not  denote  nephritis ;  and  we  should  err 


THE  THEORY  OF  THE  TREATMENT   OF   DIABETES  87 

greatly  if  we  were  to  diagnosticate  nephritis  on  this  account.  "What  is  found 
at  the  autopsy  is  the  large,  slightly  hyperemic  "  diabetic  kidney  "  which  shows 
none  of  the  changes  that  we  expect  to  find  in  nephritis. 

The  transition  of  diabetes  into  nephritis,  which  is  frequently  mentioned, 
is,  therefore,  very  questionable;  the  true  diabetic  albuminuria  of  severe  cases 
is  not  nephritic,  and  the  albuminuria  of  the  mild  cases  is  not  diabetic,  but 
frequently  due  to  an  independent  nephritis.  It  is  true  that  a  genuine  nephritic 
albuminuria  not  infrequently  takes  the  place  of  glycosuria;  for  when  the 
arterio-sclerotic  or  other  form  of  chronic  nephritis  which  may  appear  becomes 
really  severe,  the  albuminuria  becomes  more  pronounced,  whereas  the  sugar 
disappears  from  the  urine. 

IV.   THE   THEORY   OF   THE   TREATMENT   OF   DIABETES 

Diabetic  glycosuria  has  a  tendency  to  increase  during  a  decrease  in  the  patient's 
tolerance,  whereas  during  sugar-free  periods  the  tolerance  usually  increases.  Hyper- 
compensatory  hyperglycemia.  Dietetic  aglycosuxia  as  a  theoretic  postulate.  The  rela- 
tive importance  of  carbohydrates,  albumin,  fat,  and  alcohol  for  the  diabetic  Difficulties 
in  supplying  sufficient  nutrition;  temporary  undernutrition  not  always  avoidable. 
Acidosis  diabetica  with  acetonuria  and  diaceturia.  The  secondary  increase  of  albumin 
waste  and  the  secondary  decrease  of  the  powers  of  oxidation  in  diabetics.  Acidosis  an 
expression  of  the  disproportion  between  over-abundant  tissue-destruction  and  the  less- 
ened powers  of  oxidation.     Acidosis  as  a  cause  of  the  diabetic   (dyspneic)   coma. 

The  only  method  of  treatment  of  real  value  in  diabetes  is  the  dietetic. 
(We  shall  refer  later  to  the  medical   treatment.) 

The  foundation  for  the  dietetic  treatment  in  diabetes  was  laid  one  hundred 
years  ago  by  an  English  physician,  Rollo,  but  it  is  only  of  late  years  that  this 
method  of  treatment  has  become  general.  Rollo  discovered  the  correct  method 
empirically,  but,  as  is  frequently  the  ease,  the  theoretic  foundation  had  to  be 
worked  out  before  his  treatmenl  obtained  general  recognition,  and  it  required 
great  laboT  to  establish  this  theoretic  foundation.  But  it  is  nut  for  this  reason 
that  I  intend  to  enter  somewhat  more  minutely  into  these  theoretic  considera- 
tions  of   tlic   treatment    of   diabetes,    I > 1 1 1    because   we   cannot    otherwise  obtain 

such  clear  ideas  of  diabetes  a-  are  required  for  the  practice  of  medicine. 

THE  FIRST  FUNDAMENTAL  PRINCIPLE  in  the  treatment  of  diabetes  to  which 
I  refer  is  this: 

Diabetic  glycosuria  usually  increases  "'Uli  Ihm .  while  the  tolerance  of  the 
patient  decreases. 

The  tolerance  of  the  diabetic  depends  upon  the  relation  between  the 
amount  of  sugar  excreted  and  the  quantity  of  sugar  and  sugar  producer-  (par- 
t  icularly  the  carbohydrates)  ingested. 

In  the   following  example,   for  the  -ake  of  simplicity,  I  shall  estimate  the 

entire  amount  of  the  carbohydrates  in  the  fond  as  bread. 

A  patient  receives  500  grams  of  meat,  3  eggs,  ten  grams  of  vegetables  deficienl  In 
carbohydrates  (salad,  spinach,  etc.),  inn  grams  of  fat   (cheese,  sausage),  in  which  there 

i-  -nine  albumin  which  n I  col  !»•  taken  Into  account,  butter  and  fat  in  tlic  food.  100 

grams  of  wheal  bread,  100  grams  of  cream  and  the  oecessarj  wine,  coffee  and  water.    Be 

excretes  two  and  a  half  liters  of  urine,  with  3.6  per  cent,  sugar,  thai  is,  on  the  average, 


88  DIABETES  MELLITUS 

88  grams  of  sugar  per  day.  If  he  lives  for  months,  with  this  glycosuria,  it  is  to  be 
expected  that  with  the  same  nourishment  he  will  excrete  more  sugar ;  for  example,  4 
per  cent.,  that  is,  upon  an  average,  100  grams  per  day;  in  other  words,  7ms  tolerance 
(for  carbohydrates)   has  decreased. 

This  lessening  of  tolerance,  due  to  the  glycosuria,  may  not  take  place  if 
the  glycosuria  is  very  slight  and  does  not  amount  to  more  than  from  ten  to 
twenty  grams  in  a  day ;  but  in  cases  in  which  the  glycosuria  shows  such  an 
increase  as  in  the  example  just  quoted,  the  patient's  tolerance  is  bound  to 
diminish  within  a  short  time. 

The  second  fundamental  principle  which  is  a  necessary  complement 
to  that  mentioned  above  is  as  follows: 

When  the  diabetic  is  free  from  sugar,  his  tolerance  usually  increases. 

For  example,  a  diabetic  on  the  diet  previously  mentioned  excretes  88  grams  of 
sugar.  To  diminish  the  glycosuria  his  allowance  of  bread  is  reduced;  this  decrease  in 
food,  however,  is  not  sufficient ;  bread  must  be  withdrawn  entirely  to  render  the  patient 
free  from  sugar;  as  soon  as  even  ten  grams  of  bread  are  allowed  he  begins  to  excrete 
sugar  again,  although  only  from  six  to  eight  grams  per  day.  Next  the  patient  remains 
for  four  weeks  without  bread  and  his  urine  becomes  free  from  sugar.  After  this,  if  the 
physician  is  careful,  from  twenty  to  thirty  or  forty  grams  of  bread  may  gradually  be 
given  without  being  followed  by  an  excretion  of  sugar;  the  patient's  tolerance,  during 
the  sugar-free  period  of  four  weeks,  has  been  materially  improved. 

How  may  both  these  conditions  be  explained  ?  The  improvement  of  toler- 
ance during  the  sugar-free  period  exemplifies  Hoffmann's  law  that  "  by  lessen- 
ing the  work  of  any  diseased  function  the  latter  may  be  improved,"  which  law, 
however,  if  we  are  honest,  is,  in  the  case  of  diabetics,  little  more  than  a  lengthy 
statement  of  the  facts  which  are  to  be  explained. 

There  is  more  hope  of  success  in  the  attempt  to  explain  the  aggravation 
of  the  patient's  intolerance  of  carbohydrates  during  every  decided  glycosuria. 
The  amount  of  sugar  in  the  blood,  as  is  well  known,  is  quite  constant  in  man, 
at  least  it  never  falls  below  a  certain  point  (about  0.8  per  cent.)  ;  if,  for  exam- 
ple, after  severe  muscular  exertion,  sugar  almost  disappears  from  the  blood, 
a  fresh  supply  is  sent  from  the  carbohydrate  storehouse  (the  liver)  ;  this 
may  be  called  a  process  of  compensation.  If  now,  after  severe  sugar  losses, 
it  is  desirable  that  a  great  amount  of  sugar  be  quickly  brought  to  the  blood, 
it  appears  (according  to  some  facts  the  explanation  of  which  I  shall  not  give 
at  this  point)  that  a  hypercompensation  occurs.  Hence  arises  the  paradoxical 
conception  that  loss  of  sugar  produces  hyperglycemia!  If  this  seeming  para- 
dox is  really  true,  and  if  it  holds  good  even  for  the  diabetic  with  an  already 
existing  hyperglycemia,  then  a  spontaneous  increase  of  diabetic  hyperglycemia 
by  hypercompensation  becomes  comprehensible.  Therefore,  as  long  as  sugar  is 
lost  by  the  urine,  a  steady  increase  of  hyperglycemia  leading  to  a  still  greater 
glycosuria  is  to  be  expected. 

Whether  these  attempts  at  explanation  are  correct  or  not,  the  two  laws 
themselves  to  which  they  refer  are  as  near  the  truth,  I  think,  as  can  be  deter- 
mined to-day.  And  as  the  aim  of  the  therapy  of  diabetes  they  show  us  this: 
to  render  the  patient  free  from  sugar  and  to  keep  him  aglycosuric. 

This  conclusion  is  identical  with  that  arrived  at  in  the  end  of  the  last  chap- 


THE  THEORY   OF  THE  TREATMENT  OF  DIABETES  89 

tcr  regarding  the  meaning  of  diabetic  hyperglycemia.  We  there  said  that 
hyperglycemia  is  the  cause  of  most  of  the  complications  and  many  of  the 
dangers  of  diabetes  mellitus,  and  the  patient  is  safe  only  when  he  is  excreting 
little  or  no  sugar. 

Therefore,  there  can  be  no  question  that  in  every  case  of  diabetes  the 
therapeutic  indication  is  to  render  the  patient  aglycosuric,  or  sugar-free.  It 
is  obvious  that  the  treatment  is  to  be  begun  as  soon  as  possible,  so  that  little 
time  may  remain  in  which  the  disease  may  unfold  its  tendency  to  develop 
ad  pejus.  If  there  is  any  theoretical  law  as  regards  treatment  which  is  found 
to  succeed  in  practice  it  is  this.  The  chances  for  successful  treatment  are, 
ceteris  paribus,  very  much  better  in  recent  eases.  It  is  just  as  important  to 
insist  that  the  treatment  is  an  obvious  necessity  in  the  later  course  of  the 
disease,  and  should  also  be  attempted  from  the  beginning  of  symptoms  by 
means  of  dietetic  treatment.  For  it  has  been  determined  only  as  regards  the 
dietetic  treatment,  and  not  as  regards  the  aglycosuria  brought  about  by  drug 
treatment,  that  it  increases  the  tolerance  of  the  diabetic. 

There  are  no  theoretic  contra-indications  (i.e..  such  as  might  be  derived 
from  our  knowledge  of  the  diabetic  disturbances  of  metabolism)  against 
carrying  out  this  requirement,  although  the  practical  difficulties  are  fre- 
quently great. 

The  dietetic  treatment  of  the  diabetic  gains  its  end  by  forbidding  the  use 
•  if  sugar  and  sugar-producing  food-  as  far  as  possible.  Tin1  sugar-producing 
fn<, ,ls  are  the  carbohydrates  and  albumin.  Even  from  albumin  sugar  is  pro- 
duced in  animal  metabolism,  and  in  no  -mall  quantity,  as  from  100  gram-  of 
albumin  (which  amounts  to  about  loo  grams  of  raw  meat)  about  oil  gram-  of 
BUgar,  or  even  more,  may  be  formed.  It  is  important  to  note  that  the  organ- 
ism also  produces  sugar  from  those  varieties  of  albumin  which  contain  no 
preformed  sugar,  i.e..  those  from  which  it  is  impossible  to  extract  sugar  by 
chemical  mean-.  An  example  of  such  an  albumin  containing  no  preformed 
Bugar  is  casein,  and  from  this  substance  the  diabetic  produces  sugar  in  large 
amounts. 

Sugar    production    from    fat    doe-    not    play    such    an    important    role   a-    to 

influence  diabetic  glycosuria  to  any  notable  extent.  For  this  reason,  and  on 
account  of  its  high  calory  value.  fat  is  the  most  valuable  food  substance  for 
the  diabetic. 

According  to  the  very  latesi  investigations  (Bjierre)  it  may  be  looked 
upon  a-  settled  thai  alcohol  has  nutritive  value  (indeed.  1  gram  of  alcohol 
upon  oxidation  furnishes  as  much  as  :  calorie-)  and  the  diabetic  doe-  not 
form  sugar  from  this.  But  it-  utilization  a-  food  is  limited,  for  if  it  i-  admin- 
istered in  large  amounts  it  acts  a-  a  poison  to  protoplasm,  increasing  albumin 
decomposition.  It  i-  believed  thai  this  toxic  action  of  alcohol  is  to  be  feared 
when  more  than  50  grams  of  alcohol  are  taken  per  day. 

Thai  the  patient  musl  be  sufficiently  nourished,  no  matter  how  stricl  the 
diabetic  treatment,  is  a  well-known  rule,  but  by  this  we  do  not  mean  to  -ay 
that,  temporarily,  the  patient  may  not  be  subjected  t<>  hyponutrition ;  I  have 
already  spoken  of  this,  under  some  circumstances,  a-  we  -ball  see.  it  i<  even 
then  permissible  for  the  patient  to  abstain  completely  from  food  for  twenty- 


90  DIABETES  MELLITUS 

four  hours  in  order  that  his  urine  may  become  free  from  sugar.  Just  so, 
it  is  occasionally  necessary  to  give  for  a  few  days  so  little  food  that  some 
of  the  patient's  body  substance  is  utilized.  At  the  beginning  of  strict  dietetic 
cures,  it  is  often  very  difficult  to  overcome  this  consumption  of  tissue  in  dia- 
betics who  have  previously  lived  upon  a  mixed  diet  and  have  excreted  much 
sugar. 

Let  me  again  illustrate.  Imagine,  for  example,  a  man  weighing  65  kilograms,  who, 
on  a  mixed  diet,  has  been  excreting  600  grams  of  sugar  daily.  He  is  put  lipon  a  diet 
not  absolutely  free  from  carbohydrates.  According  to  Rubner,  a  man  requires  for  his 
maintenance  about  35  calories  per  kilogram,  so  that  this  man  ought  to  have  sufficient 
food  to  produce  35  X  65,  or,  in  round  numbers,  2,300  calories  daily. 

80  grams    wheat,  bread  contain  50  grams  starch  =  200  calories. 

500  boiled  or  fried  meat,  medium  fat   (5  per  cent.  )  =  750        " 

200       "        cream    (30  per  cent,  fat)  =600        " 

200       "        milk  =120 

100       "        fat,  in  butter,  cheese,  fat  sausage,  bacon,  etc.  =  900        " 


2,570  calories. 


Besides  this  we  will  add  about  300  to  400  grams  of  green  vegetables,  whose  calory 
value,  like  that  of  the  albumin  partaken  of  in  fat  foods  (bacon,  cheese,  fat  sausage,  etc.), 
may  be  disregarded. 

According  to  this  our  patient  would  be  plentifully  fed,  if  he  were  free  from  sugar, 
for  a  diabetic  who  excretes  no  sugar  does  not  emaciate,  and  consequently  does  not  need 
any  more  food  than  a  healthy  person.  Unfortunately,  our  patient  continues  on  this  diet 
to  excrete  his  full  100  grains  of  sugar  per  day.  The  calory  value  of  these  100  grains 
(400  calories)  must  be  subtracted  from  the  total  calory  value  of  the  food  he  is  ingesting; 
2,570  calories  — 400  calories  =  2,170  calories,  which  is  130  calories  less  than  the  patient 
requires,  according  to  Rubner. 

In  some  cases,  under  favorable  circumstances,  it  is  possible  to  supply  these 
missing  130  calories  by  the  further  addition  of  fat,  but  by  no  means  always; 
at  least,  under  ordinary  circumstances,  it  is  often  quite  difficult  to  make  the 
patient  take  the  500  grams  of  meat,  200  grams  of  cream  and  100  grams  of 
fat  mentioned  in  the  dietary  above;  and  we  must  always  avoid  throwing  too 
great  a  burden  upon  the  metabolism  of  the  diabetic.  In  short,  as  a  choice  of 
evils,  we  must  often  allow  our  patient  to  remain  underfed  and  lose  weight, 
until  his  excretion  of  sugar  decreases  appreciably.  Only  when  the  glycosuria 
becomes  so  slight  that  the  net  calory  value  of  the  ingested  food  approaches  the 
gross  calory  value,  can  we  expect  to  avoid  the  evil  of  under-nutrition.  We 
must  risk  under-nutrition  quite  often,  in  severe  cases,  e.  g.,  when,  in  order  to 
abolish  the  glycosuria,  we  forbid  all  bread,  and  reduce  the  albuminous  (meat) 
food  considerably. 

I  know  of  no  successful  treatment  of  severe  cases  without  temporary  under- 
nutrition, but  the  physician  must  be  very  careful  during  these  periods.  We 
should  be  especially  cautious  in  regard  to  long-continued  hyponutrition,  such 
as  entails  a  loss  of  weight  of  more  than  two  kilograms  in  subjects  who  have 
already  reached  the  minimum  weight  of  130  pounds  in  men  and  110  pounds 
in  women,  for  this  loss  is  difficult  to  regain. 

In  the  consideration  of  the  theory  of  treatment  in  diabetes,  some  mention 
of  diabetic  acidosis  will  not  be  out  of  place.    By  this  term  I  mean  the  forma- 


THR  THEORY  OF  THE  TREATMENT   OF   DIABETES  91 

tion  of  /3-oxy butyric  acid  in  the  processes  of  metabolism.     It  never  fails  to 
occur  in  serious  cases,  and  even  in  mild  cases  it  appears  quite  often. 

Acetonuria  and  diaceturia  are  part  of  acidosis,  for  both  substances,  acetone 
as  well  as  acetoacetic  acid  (diacetic  acid),  originate  from  oxybutyric  acid.  I 
must  insist  upon  this  view  which  has  many  evidences  in  its  favor,  among  them 
the  fact  that  acetonuria  and  diaceturia  only  occur  when  oxybutvrie  acid  is  also 
found  in  the  urine.  I  know  very  well  that  some  prominent  chemists  have 
maintained  the  direct  opposite,  but  I  also  know  thai  very  prominent  chemists 
may  be  mistaken  in  their  reports;  for  in  the  very  cases  in  which  they  found 
no  oxybutvrie  acid  in  spite  of  the  presence  of  acetone  and  acetoacetic  acid, 
and  in  the  specimens  which  they  kindly  sent  to  me  for  examination  in  my 
laboratory,  I  succeeded  in  demonstrating  oxybutvrie  acid  in  the  urine. 

Therefore,  acidosis,  including  acetonuria  and  diaceturia,  plays  an  impor- 
tant role  in  diabetes.  In  twenty-four  hours  oxybutyric  acid  may  be  excreted - 
in  amounts  above  100  grams,  and  acetone  -f-  diacetic  acid  up  to  15  grams. 
As  these  substances  are  easily  oxidized,  their  excretion  in  such  large  amounts 
shows  a  deficiency  in  the  power  of  oxidation  possessed  by  the  tissues  in  these 
cases  of  diabetes  mellitus.  As  regards  this  decrease  in  the  power  of  oxidation 
in  the  diabetic,  the  conditions  are  very  similar  to  those  involved  in  the  in- 
creased decomposition  of  albumin.  Neither  is  primarily  due  to  the  diabetic 
disturbances  of  metabolism,  but  since  the  albuminoid  decomposition  is  only 
increased  when  sugar  is  wasted  and  passes  out  unutilized  in  the  urine,  this 
weakness  of  oxidation  may  be  referred  to  the  lack  of  oxidation  of  sugar. 

The  oxidation  of  sugar,  however,  does  not  fail  because  the  general  power 
of  oxidation  is  diminished,  hut  vice  versa.  Since  for  other  reasons  the  sugar 
is  not  oxidized,  the  general  power  of  oxidation  becomes  lessened;  of  all  the 
products  which  are  consumed  in  the  organism,  sugar  is  the  mosl  readily  com- 
bustible, and  in  the  tire  which  thus  arises  in  normal  metabolism,  other  less 
readily  oxidizable  substances  are  consumed,  a  process  designated  by  physiolo- 
gists as  secondary  oxidation,  (»wing  to  the  Facts  just  mentioned,  the  same 
substances  which  produce  acidosis  may  occur  in  other  conditions — in  non- 
diabetic  persons  whenever  carbohydrates  and  sugar-  are  withheld  entirely. 
In  the  diabetic,  too,  they  usually  appear  when  the  carbohydrates  are  excluded 
from  the  food.  They  may  be  ex.reted.  however,  in  severe  diabetes,  with 
marked  glycosuria,  even  when  carbohydrates  are  eaten  in  large  amounts.  Here 
acidosis  indicate-  that  the  sugar  metabolism  of  the  body  bas  fallen  so  low  that 
in  spite  of  the  plentiful  ingestion  of  carbohydrate  food,  very  little  of  it  is 
consumed.  The  fire  which  lights  the  secondary  oxidation  processes  is  almost 
extinguished,  and  thus  the  total  power  of  oxidation  of  the  organism  Is  dam- 
aged. It  mu-t  be  remembered  that  this  condition  is  due  to  the  disproportion 
between  the  product-  ready  for  oxidation  in  metabolism  and  the  power  of 
oxidation,     in  diabetic  patient-  ti--ue  decomposition  goes  on  too  rapidly  for 

their  power  of  oxidation  ;  their  noiiri-hmeiit   i-  both  improper  and  too  |>rofu-e. 
yet   by  limitation  of  their  metabolism  and  careful   diel    it    LS  often   possible  to 

re-tore  to  par  the  power  of  oxidation,  and  thus  cause  the  acidosis  to  disappear. 
It  has  been  necessary  to  discuss  acidosis  quite  in  detail  because  of  it- 
role  in  diabetic  coma.    Acidosis  is  the  only  certainly  known  cause  of  this  conia 


92  DIABETES  MELLITUS 

(that  is,  of  many  cases  of  it).  We  now  recognize  that  it  is  oxybutyric  acid 
which  produces  true  dyspneic  coma;  that  is,  an  acid  coma,  i.  e.,  a  coma  which 
is  an  expression  of  an  over-acid  condition  of  the  blood,  and  this  hyperacidity 
is  due  to  the  presence  of  a  large  amount  of  oxybutyric  acid  (100  grams  or 
more),  which  is  formed  and  which  enters  the  blood  within  twenty-four  hours. 
This  fact,  and  also  the  danger  that  by  a  too  rapid  withdrawal  of  carbohydrates 
one  may  cause  acidosis,  as  well  as  coma,  renders  it  necessary  for  the  physician 
to  be  familiar  with  this  process. 

V.    PRACTICAL   THERAPY 

Every  therapeutic  measure  is  to  be  used,  but  after  the  dietetic  treatment  mineral 
waters  alone  are  of  much  service.  Prophylaxis ;  obesity  and  diabetes  mellitus.  From 
the  point  of  view  of  dietetic  treatment,  three  forms  of  diabetes  are  to  be  distinguished: 
the  medium  severe,  the  mild,  and  the  severe.  The  medium  severe  cases,  their  diagnosis 
and  their  importance  in  practice.  The  aim  of  treatment  in  cases  of  each  form.  For  the 
proper  dietetic  treatment  of  every  case  a  quantitative  and  qualitative  estimate  of  the 
entire  dietary  is  necessary.  Preliminaries  of  treatment :  Quantitative  regulation  without 
limitation;  its  result.  Further  steps  toward  the  abolition  of  glycosuria  and  improve- 
ment of  tolerance,  maximal  reduction  of  albuminous  food  and  the  twenty-four-hour  fast. 
Diet  lists  for  the  diabetic;  there  are  no  foods  absolutely  permissible.  Carbohydrate 
nutrition :  Bread,  cereals,  vegetables,  fruits ;  calculation  of  their  relative  advantages 
and  dangers.  Meat,  fish,  and  eggs.  Fatty  foods.  Sausage,  cheese,  bacon,  butter,  oil, 
cream.  Drinks:  Milk,  wine,  beer,  whiskey,  tea,  coffee.  Artificial  foods.  Hospital  treat- 
ment. Dispensary  treatment  and  "  bath-cures."  Disturbances  and  dangers  arising  during 
the  treatment  of  diabetes. 

I  wish  to  speak  first  and  chiefly  of  the  dietetic  treatment  of  diabetes,  but 
of  course  every  other  therapeutic  measure  is  to  be  welcomed  and  utilized.  It 
should  not  be  forgotten  that  since  almost  any  disturbance  of  a  diabetic's  gen- 
eral health  tends  to  aggravate  the  underlying  disease,  common  sense  teaches  us 
to  treat  as  carefully  as  we  can  any  minor  ailment  from  which  the  patient 
may  suffer  from  time  to  time.  If  he  is  syphilitic,  carefully  planned  specific 
treatment  should  be  used,  as  also  quinin  in  malaria,  digitalis  in  circulatory 
disturbances,  and  appropriate  treatment  for  nervous  affections.  By  such  treat- 
ment we  may  succeed  in  improving  but,  unfortunately,  very  rarely  in  curing 
the  diabetes — that  is  to  say,  the  glycosuria  and  the  other  symptoms  which 
may  be  dependent  on  it. 

It  is  just  as  evident  that  the  treatment  of  diabetes  must  always  be  a 
treatment  of  the  entire  organism,  i.  e.,  that  the  mode  of  life  of  the  patient 
must  be  properly  arranged  in  all  respects.  From  this  standpoint,  there  are 
two  factors  to  be  considered — mental  and  emotional  rest,  and  sufficient 
muscular  exercise;  I  say  sufficient  muscular  exercise,  but  no  more,  for  too 
much  readily  increases  the  glycosuria. 

The  main  point,  however,  the  alpha  and  omega  in  the  care  of  the  diabetic, 
is  the  dietetic  treatment;  besides  this,  mineral  water  cures  (Carlsbad,  Neue- 
nahr.  Vichy)  also  play  a  role,  bvt  not  drugs.  There  is  scarcely  a  physician 
familiar  with  diabetes  who  will  resort  to  drugs  to  diminish  the  glycosuria.  It 
is  true  there  are  many  remedies  which  bring  this  about,  and  among  them 
some  which  produce  this  effect  without  diminishing  the  demand  for  food  or 


PRACTICAL  THERAPY  93 

the  actual  intake  of  nourishment.  But — they  act  only  in  those  cases  in  which 
the  dietetic  treatment  alone  would  suffice,  and  in  which  they  are,  therefore, 
superfluous.  During  the  administration  of  drugs  (if  we  do  use  them)  the 
dietetic  treat  incut  should  never  he  forgotten,  else  the  case  will  fail  to  do  well 
in  the  long  run.  For  a  few  weeks,  perhaps,  here  and  there,  by  the  adminis- 
tration of  opium,  occasionally  also  by  the  use  of  antipyrin  and  other  nervines, 
the  glycosuria  may  be  limited  or  even  removed.  Then  the  action  of  these  drugs 
ceases  and  glycosuria  returns  to  its  former  height,  sometimes  even  exceeding 
it.  It  appears,  as  I  have  already  indicated,  that  the  tolerance  of  the  diabetic 
is  not  improved  by  a  drug  diminution  of  glycosuria;  and  even  in  an  agly- 
cosuric  condition,  in  case  this  is  brought  about  by  drugs,  the  patient's  toler- 
ance does  not  improve  as  it  does  under  diet. 

That  we  shall  ever  find  a  specific  remedy  for  diabetes,  musl  be  regarded 
as  quite  unlikely,  especially  by  those  who.  like  myself,  look  upon  the  disease 
as  an  expression  of  hereditary  weakness  of  metabolism;  at  present  we  cer- 
tainly do  not  possess  such  a  remedy. 

We  shall  now  proceed  to  the  discussion  of  the  dietetic  treatment  in  detail. 

This  method  of  treatment  has  its  place  qo!  only  in  the  care  of  confirmed, 
true  diabetes  mellitus,  but  also  in  prophylaads. 

In  families  in  whom  this  disease  is  hereditary  there  should  be  great  mod- 
eration in  the  use  of  carbohydrates  in  any  form,  i.e.,  limitation  of  the  sugar 
metabolism  should  be  made  an  unalterable  law.  But  there  should  also  be 
moderation  in  eating  and  drinking  in  general.  There  can  be  no  doubt  that 
habitual  hypernutrition  favors  the  outbreak  of  diabetes  if  the  predisposition 
to  it  exists.  The  cases  of  diabetes  mellitus  complicating  obesity  (even  in 
full-blooded  individuals  with  arteriosclerosis)  are  almost  all  to  be  included  in 
this  category.  Alcoholism,  at  least  thai  form  thai  goes  band  in  hand  with 
over-nutrition,  also  plays  a  part  in  the  etiology  of  diabetes. 

In  individuals  with  a  hereditary  predisposition  and  marked  obesity  due  to 
over-nutrition,  diabetes  should  always  be  watched  for.  and  an  occasional  exam- 
ination be  made  of  tlie  urine  voided  four  hours  after  a  breakfast  in  which  at 
least  100  grams  of  bread  and  about  30  grams  of  sugar  have  been  consumed: 
or.  for  greater  certainty,  a  tesl  for  glycosuria  alimentaria  e  saccharo  should 
be  made,  ami  the  ease  should  then  be  judged  with  the  necessary  reserve. 

In  confirmed  diabetes,  dietetic  therapy  has  for  its  object  the  elimination 
of  glycosuria  if  possible.  This  occurs  very  readily  in  some  cases,  in  others  it 
is  difficult,  and  in  Bome  it  may  be  impossible;  even  when  it  may  be  accom- 
plished, although  with  difficulty,  there  are,  unfortunately,  many  case-;  in  which 
the  results  scarcely  compensate  the  physician  and  patient    for  the  required 

trouble. 

The  amount  of  energy  thai  Bhould  be  put  into  the  treatment  varies  in 
differenl  cases,  and  much  labor  will  be  saved  the  physician  and  the  patient 
if  this  fact  is  recognized  from  the  onsel  ;  on  tin-  accounl  it   i-  convenienl  to 

divide  diabetics  into  three  group-,  a  method  which  I  proposed  ten  year-  ago. 

1.  The  moderately  severe  cases. 

2.  The  mild  cases. 

3.  The  Bevere  or  very  Bevere  cases. 


94  DIABETES  MELLITUS 

We  have  already  learned  to  differentiate  between  mild  and  severe  cases, 
but  in  ganging  the  case  from  a  therapeutic  standpoint  we  need  to  recognize 
also  a  group  of  moderately  severe  cases.  The  mild  cases  are  so  benign  that 
they  offer  a  splendid  prospect  for  therapy  and  usually  require  but  little  treat- 
ment. The  severe  and  very  severe  cases,  on  the  other  hand,  are  so  malignant 
that  even  after  the  most  energetic  therapy  the  results  obtained  are  slight  and 
unsatisfactory  because  incomplete  or  transitory.  In  the  group  of  moderately 
severe  cases  are  included  a  great  many  which  occupy  a  middle  position,  being 
by  no  means  so  benign  that  they  do  not  recpiire  continued  observation  and 
proper  treatment,  but  by  no  means  so  malignant  that  they  should  be  left  to 
their  fate;  by  a  more  or  less  strict  plan  of  treatment,  they  may  be  preserved 
in  fair  health  and  moderate  activity  for  many  years.  Among  the  cases  which 
at  the  beginning  of  treatment  must  be  included  in  this  intermediate  group, 
there  are  not  a  few  which  prove  to  belong  to  the  mild  form,  but  which,  on 
account  of  unfavorable  influences,  have  passed  temporarily  into  the  moder- 
ately severe  form.  In  this  group  we  also  find  some  which  belong  to  the  severe 
or  very  severe  forms,  but  have  not  yet  reached  the  full  development  of  the 
disease. 

Let  us  illustrate: 

A  man  aged  fifty,  with  an  inherited  predisposition  to  diabetes.  Ten  days  previously, 
he  undertook  a  lengthy  and  fatiguing  excursion  in  the  Black  Forest,  ate  and  drank  more 
than  usual,  and  was  thoroughly  drenched  by  a  heavy  rain.  Since  that  time,  he  has  had 
a  voracious  appetite,  extreme  thirst,  marked  diuresis,  and  has  lost  much  weight.  His 
urine  contained  8  per  cent,  of  sugar  (  !  ) .  His  daily  dietary  was  restricted  quantitatively 
to  about  one  pound  of  meat,  several  eggs,  coffee  with  rich  cream  but  no  sugar,  green 
vegetables  (no  potatoes  or  beets),  no  cereals,  80  grams  only  of  wheat  bread,  his  meals 
to  be  prepared  without  flour;  one  bottle  of  wine  was  allowed.  Within  a  few  days  his 
glycosuria  had  disappeared.  The  case  has  continued  to  run  a  mild  course  up  to  the 
present  time  (twelve  years  subsequently).  Since  the  acute  attack,  the  patient's  diet, 
for  the  most  part,  has  been  restricted  as  above,  although  at  times  it  has  been  relaxed 
to  the  extent  of  allowing  sweet  champagne;  the  sugar  in  the  urine  has  never  risen  above 
0.5  per  cent. 

At  the  beginning  of  treatment  this  case  appeared  very  desperate,  but  it 
soon  became  a  clear  example  of  the  mild  form  of  diabetes. 
To  illustrate  again : 

A  peasant,  thirty-three  years  of  age  and  of  a  diabetic  family.  For  five  weeks  following 
an  accident  he  complained  of  hunger,  thirst,  loss  of  flesh,  lassitude,  and  cramps  in  the 
calves  of  his  legs.  Patellar  reflexes  present;  no  complications;  weight  48  kilograms; 
internal  organs  sound.  After  eight  days  on  regulated  diet  including  fat  meat,  with  150 
grams  of  milk,  and  20  grams  of  wheat  bread,  the  sugar  in  his  urine  was  still  4  per  cent. 
-  5  per  cent.  (75  to  100  grams  of  sugar  a  day).  Only  after  the  complete  withdrawal  of 
bread  and  increase  of  milk  to  200  grams  did  the  urine  gradually  become  free  from  sugar. 
After  this  on  a  diet  with  200  grams  of  milk  and  50  grams  of  bread  he  remained  aglyco- 
suric  for  several  months,  but  even  then  he  had  to  rigidly  conform  to  rules  in  order  to 
prevent  tli<-  reappearance  of  glycosuria.  In  this  fashion  he  has  now  lived  for  years.  His 
weight  is  5G  kilograms. 

This  is  a  typical  case  of  the  medium  severe  form;  severe  at  its  onset  but 
under  continuous,  moderately  strict  dietetic  treatment  taking  a  rather  favor- 
able course. 


PRACTICAL  THERAPY  95 

The  following  is  another  typical  example  of  this  group: 

A  bookbinder,  seventeen  years  old.  No  family  history  of  diabetes.  For  five  weeks, 
without  apparent  cause,  he  was  continually  hungry,  he  lost  weight,  was  extremely  weak, 
and  liad  a  non-gonorrheal  urethritis.  Organs  sound;  knee-jerk  normal;  weight  45  kilo- 
grains.  On  a  diet  of  220  to  300  grams  of  meat,  green  vegetables,  250  grams  of  milk  and 
300  grams  of  bread,  there  was  a  glycosuria  of  G  per  cent.  =  150  to  200  grams  of  sugar 
a  day.  Only  upon  complete  withdrawal  of  bread  while  still  taking  25  grams  of  milk, 
did  he  become  free  from  sugar.  After  a  sugar-free  period  of  one  month,  he  could  take 
more  milk  and  a  small  quantity  of  bread  without  excreting  sugar.  Be  gradually  became 
accustomed  to  a  larger  allowance  of  bread  and  milk,  being  careful  never  to  take  enough 
to  produce  glycosuria.  This  tolerance  gradually  increased  until  he  could  ingest  170 
grams  of  bread  and  100  grams  of  milk  without  sugar  appearing  in  the  urine. 

The  patient  remained  in  this  condition,  outside  the  hospital,  for  two  years.  After 
this  (probably  because  he  did  not  adhere  to  the  same  diet  i  sugar  was  again  excreted, 
and  did  not  disappear  on  very  strict  diet — so  that  the  case  became  severe. 

The  object  in  quoting  these  examples  is  to  show  clearly  the  existence  of 
a  moderately  severe  form  of  the  disease.  At  the  outset,  cases  like  those  just 
quoted  may  readily  be  looked  upon  as  extreme,  and  thus  great  harm  may 
result.  Among  the  points  on  which  the  recognition  of  medium  severe  cases 
rests  tin-  most  important  is  this,  that  after  partial  withdrawal  of  carbohydrates 
(for  example,  200  grams  of  milk  and  50  grams  of  bread),  no  matter  how 
marked  the  glycosuria  has  previously  been,  it  immediately  and  decidedly 
decreases,  usually  falling  below  lno  grams.     Besides,  in  the-«'  cases  of  medium 

pity,  the  amount  of  acidosis  as  determined  by  tin-  ferric-chlorid  and  ace- 
tone reaction  is  slight,  and  the  amount  of  urine  is  not  great  (  I  and.  at  most, 
5  liters  per  day).     All  these  conditions  may  also  exist  in  severe  cases. 

Aiter  determining  to  which  group  a  given  case  belongs,  the  physician  must 
outline  the  method  of  treatment  as  follow-: 

1.  Mild  cases  are  to  bo  made  aglycosuric,  and  maintained  in  this  condition 
until  continuous  observation  for  at  Leasl  six  months  has  demonstrated  that 
the  disease  shows  no  tendency  to  progress.  Later,  a  permanent  increase  of 
glycosuria  above  0.5  per  cent,  should  not  be  permitted.  Such  a  transitory 
increase  need  cause  no  anxiety,  hut  as  soon  as  it  becomes  greater  the  case  is 
to  be  treated  as  at  first  by  strict  limitation  of  the  diet. 

2.  Cases  of  the  medium  severe  form  are  tu  he  made  aglycosuric  by  strict 
treatment  if  tins  is  necessary.  Then,  in  case  they  do  nut  prove  to  he  mild 
cases,  they  are  to  be  permanently  maintained  in  tin-  condition.  Even  a  mild 
glycosuria  is  not  to  he  permitted,  and  anything  causing  a  transitory  increase 
of  glycosuria  is  to  be  absolutely  avoided,  as  it  threatens  the  already  greatly 
endangered  tolerance.  It  is  possible  that  there  are  individual  cases  which 
at  the  onset  belong  to  the  medium  Bevere  group,  but  which  may  be  rendered 
mild,  ami  then  the  indulgences  possible  for  cases  of  the  mild  forms  may  he 
permitted;  but  such  cases  are  certainly  not  frequent. 

•  !.  The  nature  of  the  severe  and  very  severe  cases  becomes  manifest  when 
on  the  first  attempt  to  produce  aglycosuria  the  feebleness  of  their  tolerance 
appeaiv-.  In  these  cases,  our  primary  objeel  is  to  bring  the  patient  to  the 
point  at  which  life  can  he  maintained  without  a  deficit;  but  this  can  rarely 
he  brought  about,  unless  we  can  limit,  and  that  decidedly.  th(  -ugar  in 


96  DIABETES  MELLITUS 

the  urine.  We  must  make  an  attempt  to  diminish  the  glycosuria,  and  see  now 
far  we  are  successful.  Xow  and  then,  Ave  can  accomplish  more  than  we  had 
hoped,  and  a  better  tolerance  may  follow  a  regulation  of  the  diet  and  a  reduc- 
tion of  the  glycosuria,  so  that  we  may  succeed  in  maintaining  the  patient's 
equilibrium  of  metabolism  with  a  very  slight  glycosuria  and  with  a  fair  con- 
dition of  health  for  years,  even  after  all  hope  had  seemed  to  be  gone. 

This  is  the  chief  task  of  the  physician,  easy  in  some  cases,  more  difficult 
in  others,  and  in  many  almost  impossible.  Although  the  treatment  of  the 
different  groups  of  cases  varies,  one  general  rule  applies  to  all.  We  should 
determine  the  exact  quantitative  and  qualitative  diet  for  every  diabetic  who 
comes  under  treatment.  Prout  exaggerated  when  he  stated  (1820)  that  the 
quantity  of  the  food,  that  is,  the  quantitative  restriction,  is  more  important 
for  the  diabetic  than  its  quality;  but  his  maxim  that  all  of  the  diabetic's  food 
(including  meat)  is  to  be  determined  quantitatively,  holds  good,  because  noth- 
ing more  unfortunate  can  befall  a  diabetic  than  the  overtaxing  of  his  general 
powers  of  metabolism.  I  consider  the  restriction  of  labor  of  the  whole  metab- 
olism to  be  an  important  advance  in  the  therapy  of  diabetes.  There  are  no 
foods  which  the  diabetic  can  be  allowed  to  eat  in  unrestricted  amount;  the 
quantity  of  each  must  be  measured.  We  must  see  that  he  does  not  get  too 
much  carbohydrate  food,  or  too  much  animal  food,  and  that  he  has  just  enough 
fat,  neither  too  much  nor  too  little. 

I  am  proceeding  on  the  supposition  that  the  patient  is  to  be  treated  not 
in  a  hospital  but  in  his  own  home.  First  of  all,  we  must  determine  quantita- 
tively for  several  days  the  amount  of  each  food  ingested.  For  this  purpose  it 
is  only  necessary  to  know  the  amount  of  each  carbohydrate  (flour,  bread, 
sugar  and  milk)  used  in  the  preparation  of  his  meals.  If  this  plan  is  carried 
out,  there  is  no  difficulty  later.  Fach  variety  of  food  should  be  served  on  a 
separate  plate,  and  the  amount  weighed.  Sauces  are  not  considered,  and  bread 
is  weighed  separately.  If  the  patient  cannot  afford  this,  or  if  he  is  unwilling 
to  do  it,  he  should  either  go  to  a  hospital  where  others  will  look  after  his  food, 
or  we  must  relinquish  the  attempt  to  regulate  the  whole  diet  quantitatively. 
We  may  be  able  to  get  along  without  weighing  the  food  in  very  mild  cases  in 
which  a  moderate  reduction  of  the  carbohydrates  is  sufficient  to  control  the 
disease. 

Still,  most  patients,  even  those  in  limited  circumstances,  can  arrange  to 
weigh  their  food.  Usually  a  simple  quantitative  regulation  of  the  diet,  with 
liberal  allowance  for  the  wishes  and  inclination  of  the  patient,  and  without 
too  strict  limitation,  may  be  followed  by  good,  even  remarkably  good  results; 
at  any  rate,  we  may  thus  ascertain  the  maximum  of  the  glycosuria  on  a  given 
diet  and  thus  establish  the  necessary  basis  for  further  dietary  regulations. 

An  example  will  best  serve  to  make  this  intelligible. 

A  woman,  forty  years  of  age,  no  hereditary  history  obtainable,  has  suffered  for  four 
months  from  extreme  hunger  and  thirst;  there  is  copious  diuresis;  loss  of  weight  20 
kilograms.  Present  weight  58  kilograms;  no  organic  disturbances  or  complications;  no 
acidosis;  reflexes  normal.  The  patient  asserts  that  she  has  been  on  a  diet,  that  is,  that 
she  has  eaten  but  little  bread,  etc.  During  the  first  three  days  of  treatment,  she  ate  as 
before  and  was  found  to  be  excreting  2i  to  3  liters  of  urine  with  6  per  cent,  to  7  per  cent. 
(=150  to  200  grams)   of  sugar  per  day.     Then  the  diet  was  regulated  quantitatively, 


PRACTICAL  THERAPY  97 

taking  the  wishes  of  the  patient  into  consideration.  She  received  daily  500  grams  of 
milk,  100  grams  of  bread,  200  grams  of  meat,  4  eggs,  200  grams  of  vegetables  with  ten 
per  cent,  of  fat,  50  grams  of  butter,  and  75  grama  of  fatty  cheese  or  sausage,  etc..  with 
tea,  coffee,  and  water  ad  libitum,  and  a  half  liter  of  wine.  This  diet  was  abundant,  and 
gave  the  patient  35  calories  per  kilo  of  body-weight.  She  remarked  that  she  had  not 
eaten  much  more  before  treatment,  not  even  of  bread.  During  the  following  days  she 
excreted  H  to  2  liters  of  urine,  and  3.5  per  cent.  (=50-70  grams)  of  sugar  daily.  At 
the  'same  time  she  felt  stronger  and  improved  each  day.     No  acidosis. 

This  is,  in  itself,  a  truly  remarkable  result  of  quantitative  regulation  of 
the  diet.  Of  course,  there  was  some  restriction,  but  the  patient  hardly 
noticed  it. 

In  this  case,  the  milk  and  the  bread  must  be  still  further  reduced  until 
the  sugar  has  disappeared  entirely. 

Our  patient  preferred  not  to  have  the  milk  in  her  diet  reduced.  The  bread  was  there- 
fore reduced  to  40  grams,  but  after  four  days  upon  a  diet  containing  60  grams  of  bread 
she  still  excreted  sugar,  but  when  the  milk  was  reduced  to  300  grams  and  the  bread  to 
40  grams  there  was  no  glycosuria.  On  this  diet  she  remained  aglycosuric,  so  that  after 
fourteen  days  it  was  deemed  possible  to  increase  her  food.  For  the  sake  of  precaution, 
100  grams  of  milk  were  withdrawn,  but  10  grams  of  bread  were  added,  she  remained 
free  from  BUgar.  After  three  days  100  grams  of  milk  were  added,  and  the  patient 
continued  free  from  sugar;  again  after  three  days  10  grams  of  bread  were  added,  and 
100  grains  of  milk  withdrawn.  Thus  she  continued  upon  a  diet  of  500  grams  of  milk 
and  100  grams  of  bread  for  six  weeks,  when  she  was  aglycosuric  and  in  apparent  full 
health,  having  attained  a  weight  of  62  kilograms. 

she  remained  under  observation.  Occasionally,  as  the  result  of  an  indiscretion  in 
diet,  a  Blight,  transitory  glycosuria  occurred,  and  then  the  patient  would  live  on  50 
grams  of  bread  for  a  few  days,  or  would  desist  altogether  from  eating  bread  for  a  whole 
day,  then  return  to  50  grams  of  bread  for  a  few  days,  until  finally  she  became  perfectly 
aglycosuric  on  a  diet  of  100  grams  of  bread. 

The  removal  of  glycosuria  is  by  no  means  always  bo  easy  and  -imple. 
Very  often  more  stringent  methods  must  be  employed;  carbohydrates,  flour 
foods,  and  even  milk,  must  be  wholly  excluded  before  the  patient  becomes 
entirely  free  from  sugar,  ami  frequently  even  this  is  insufficient  ami  nothing 
remains  but  the  reduction  of  albuminous  food.  The  albumin  nutrition  may 
then  be  restricted  to  200  grams,  even  to  150  grams  of  cooked  meat  (reckoning 
albumin  as  meat),  so  that  the  patient  does  not  receive  more  than  10  to  50 
grams  of  albumin.  In  the  severe  cases  this  limitation  of  the  albumin  nour- 
ishment is  one  of  the  most  important  points.  It-  effeel  is  often  much  greater 
than  can  be  explained  by  the  withdrawal  of  the  ~n ltjit  formed  from  the  albu- 
min. For  example:  With  ion  grams  of  albumin  (besides  the  accessary  fat) 
10  grams  of  sugar  are  excreted;  after  a  reduction  to  60  grams  of  albumin. 
Bugar  disappears  in  a  few  days.  That  i<>  grams  of  sugar  are  formed  from  10 
grams  of  albumin  i-  hardly  possible;  therefore,  the  aglycosuria  cannot  be  dm1 

to  the  limitation  of  BUgar  intake   (in  albumin).      1   have  long  borm  convinced 

that  it  i-  the  limitation  of  food  ami  the  resulting  disencumbrance  of  the 
entire  metabolism  which  brings  about  this  favorable  result.    The  metabolism 

of  the  diabetic  is  not  deficient  in  only  one  respect,  namely,  that  with  which 
we  are  concerned,  the  working  up  of  the  BUgar  molecule  and   it-  preparation 

for  oxidation.  His  metabolism  i-  deficient  a-  a  who!« — witness  the  weakness 
of  the  powers  <>f  oxidation  a-  expressed  unmistakably  in  the  acid 

8 


98  DIABETES  MELLITUS 

In  the  severe  cases  which  we  are  now  considering  it  is  almost  always  neces- 
sary to  limit  the  entire  amount  of  food  (albumin  and  fat  included)  so  that 
its  total  calory  value  will  be  lowered,  even  below  the  minimum  required  by 
Eubner  (35  calories  per  kilo  of  body-weight).  Under-nutrition  need  not  be 
feared;  my  diabetics,  at  least  those  who  are  treated  in  the  hospital,  get  along 
with  30  calories,  and  even  less,  per  kilo,  without  losing  body-weight. 

When  the  excretion  of  sugar  has  fallen  to  the  minimum,  about  0.5  per 
cent.,  and  not  more  than  10  grams  of  sugar  per  day  are  excreted,  aglycosuria 
may  finally  be  brought  about  by  giving  the  patient  no  food  for  twenty-four 
hours.  He  may  be  allowed  water  ad  libitum,  for  it  is  unnecessary  in  this  con- 
dition that  the  patient  should  suffer  from  thirst.  This  procedure — a  twenty- 
four-hour  fast — was  introduced  by  Cantani. 

Both  the  reduction  of  the  albuminous  foods  and  the  twenty-four-hour  fast 
seem  cruel,  or  at  least  drastic,  measures,  but  they  really  are  not  so;  at  least 
the  author  has  never  had  the  least  difficulty  in  enforcing  them.  More  diffi- 
culty in  the  strict  dietetic  treatment  of  diabetes  is  encountered  in  other  direc- 
tions.    We  shall  speak  of  this  later  on. 

After  glycosuria  has  been  abolished,  if  we  expect  to  increase  the  tolerance, 
we  must  maintain  aglycosuria  for  at  least  two  weeks  before  we  can  appreciably 
add  to  the  food.  After  the  patient  has  been  finally  brought  to  the  daily  allow- 
ance of  food  which  is  sufficient  for  him  he  must  remain  upon  this  diet  and 
be  under  observation.  It  is  also  advisable  at  times  to  institute  once  a  week 
a  twenty-four-hour  fast  for  carbohydrates,  during  which  period  the  patient 
receives  no  bread. 

Keeping  the  patient  for  a  month  or  longer  without  bread,  starchy  foods 
or  milk  rarely  succeeds,  but  the  author  knows  of  several  diabetics  who  have 
lived  for  years  on  a  strict  albumin-fat  diet  with  the  addition  daily  of  200 
to  400  grams  of  green  vegetables  (deficient  in  carbohydrates),  and  they  have 
been  able  to  attend  to  their  business  without  taking  unusual  care  of  them- 
selves. One,  a  man  about  forty  years  of  age,  held  the  responsible  position  of 
professor  at  a  university. 

We  must,  then,  exert  all  our  efforts  and  all  our  art  properly  to  regulate 
the  diet! 

In  what  follows,  I  shall  only  mention  briefly  some  of  the  main  rules,  the 
observance  of  which  will  enable  the  physician  judiciously  to  handle  his  dia- 
betics. We  shall  see,  however,  that  in  order  to  prescribe  a  diet,  he  must  be 
familiar  with  the  composition  of  the  most  common  foods  as  regards  fat  and 
carbohydrates.  All  recent  books  on  diabetes  contain  detailed  data  on  this 
subject,  and  the  most  essential  figures  in  this  respect  will  be  given  at  the 
conclusion  of  this  article. 

I  shall  attempt  no  distinction  between  what  is  absolutely  (in  any  quan- 
tity) allowable  for  a  diabetic,  and  what  is  absolutely  forbidden.  I  consider 
such  a  distinction  wrong  and  dangerous.  No  diabetic  should  be  permitted 
the  unrestricted  use  of  any  food;  everything  must  be  ordered  him  quantita- 
tively. 

The  amount  of  carbohydrates  permitted  is  best  considered  in  terms  of 
wheat  bread;  and  most  patients  prefer  to  take  the  amount  of  carbohydrates 


PRACTICAL  THERAPY  99 

permitted  them  in  the  form  of  good  wheat  bread.  Some,  however,  would 
rather  have  it  as  flour-cakes,  and  there  is  no  objection  to  their  having  it  in 
the  form  of  any  simple  carbohydrate  that  they  prefer.-  If  the  patients  take 
their  carbohydrates  partly  as  wheat  bread  and  partly  in  some  other  way.  then 
we  must  subtract  the  latter  amount  from  the  total  that  is  permissible.  Sup- 
pose, for  instance,  that  the  patient  is  allowed  LOO  grams  of  wheat  bread  = 
about  60  grams  of  starch.  He  prefers  to  take  part  of  his  starch  in  another 
form,  for  instance,  as  oatmeal  or  rice,  in  soup.  10  grams  being  sufficient  to 
make  a  large  dish  of  ^  of  a  liter;  or  he  takes  balls  of  oatmeal,  or  25  grams  of 
oatmeal  alone.  Oatmeal  and  rice  contain  about  75  per  cent,  of  starch.  We 
can  consider  the  10  grams  of  oatmeal  as  equivalent  to  wheat  bread,  and  there- 
fore we  must  subtract  10  grams  (or  to  be  quite  accurate  12  grams)  from  the 
daily  allowance  (  LOO  grams)  of  wheat  bread.  Twenty-five  grams  of  grits  or 
rice  are  equal  to  about  30  grams  of  wheat  bread.  Of  course,  the  patient  may 
have  other  form-  of  bread  instead  of  wheat  bread.  Rolls  are  useful  for  this 
purpose,  the  amount  of  starch  being  almost  the  same  as  in  wheat  bread.  The 
rolls  may  be  cut  into  small  slices  and  spread  with  butter.  Rye  bread  is  also 
serviceable;  it  contains  15  per  cent,  less  of  starch,  but  is  heavier  and  more 
compact.  Aleuronat  bread  contains  only  about  half  as  much  starch  as  wheat 
bread,  but  there  are  fvw  diabetics  who  like  this  bread,  although  among  all  the 
varieties  of  so-called  "diabetic  bread."  this  has  the  most  agreeable  taste. 

Among  vegetables  the  diabetic  should  eat  only  those  in  which  the  amount 
of  carbohydrates  does  not  exceed  5  per  cent,  (compare  the  tables),  and  even 
this  slight  amount  of  carbohydrates  must  not  be  ignored  in  those  cases  in 
which  the  removal  of  glycosuria  is  difficult.  With  300  grams  of  vegetables 
per  day,  it  may  amount  to  as  much  as  15  gram-. 

Fruits  should  be  permitted  the  diabetic  if  possible.  There  are  plenty  of 
fruits  whose  carbohydrate-,  do  not  exceed  6  per  cent,  (sugar  -f-  pectin).  They 
mii-t  be  well  cooked  and  sweetened  with  saccharin.  Almost  any  kind  of  fruit 
may  be  given,  even  such  as  contain  sugar  in  lame  amounts,  but  the  amount 

arbohydrates  they  contain  must  be  deducted  from  the  amount  of  bread 
which  is  permitted.  Only  grapes  and  dried  fruits,  on  account  of  their  high 
sugar-contents,  are  l"  be  excluded.  The  facl  that  the  sugar  contained  in  fruit 
is  levulose  modifies  the  case  but  little,  for  after  prolonged  use  levulose  becomes 
almosl  as  injurious  as  dextrose.  Many  so-called  "fruit-  for  diabetic-'*  are  to 
be  found  on  the  market  ;  they  contain  about  2  per  cent,  to  I  per  cent,  of  BUgar, 
therefore  less  than  the  fresh  fruits,  even  those  poor  in  sugar,  but,  unfortu- 
nately, many  diabetics  grow  tired  of  them  after  a  time. 

In  meat,  besides  the  albumin,  we  must  take  into  account  the  fat  it  eon- 
fain-.  Considering  only  the  percentage  of  albumin  (25  per  cent.),  the  calory 
value  of  stewed  or  broiled  meat  is  only  1.  When  the  ordinary  amount  of  fat 
is  presenl  (in  per  cent.)  the  calory  value  becomes  '.'.  but  we  mu-t  remember 
that  in  the  cooking  of  meat  (broiling,  Btewing)  part  of  the  fal  is  lost  :  in  fact, 
mos!  of  the  fal  is  lost  in  cooking.  Excluding  the  fat,  all  kinds  of  meat  are 
of  the  same  calory  value.  Liver  is  strictly  forbidden;  of  other  "'gland-" 
Bweetbreads  and  brain,  though  not  strictly  meat,  are  of  equal  value  on  account 
Of  their  high  percentage  of  fat.      Naturally,   fat   meat   i-  always  preferable  for 


100  DIABETES  MELLITUS 

a  diabetic;  some  fat  meats  and  fat  fish  contain  20  per  cent,  of  fat  or  more  (see 
diet  lists). 

As  a  working  principle,  let  us  say  that  a  diabetic  should  not  eat  more  than 
500  grams  of  meat  (weighed  after  coohing),  for  most  patients  lose  their  appe- 
tite if  they  eat  more;  diabetics  who  are  under  close  medical  supervision  may 
be  permitted  more,  but  it  is  usually  of  no  benefit. 

Eggs  are  very  useful.  On  account  of  the  large  amount  of  fat  in  the  yolk, 
each  egg  has  a  value  of  75  calories.  If  we  allow  more  than  two  eggs,  we 
'should  subtract  50  grams  for  each  egg  from  the  amount  of  meat  allowed. 

Fat  foods  are  of  the  greatest  value,  for  fat,  as  a  rule,  does  not  increase 
glycosuria  and  has  the  enormous  nutritive  value  of  9  calories,  while  starch 
and  albumin  have  only  4.  In  good  sausage  (poor  sausage  often  contains 
flour  and  but  little  fat!)  there  is  30  per  cent,  to  40  per  cent,  of  fat;  in  good 
cheese  from  20  per  cent,  to  30  per  cent. ;  poor  cheese  contains  out  little  fat. 
Butter  contains  85  per  cent,  of  fat;  lard  (butter  or  fat  melted),  bone  marrow, 
and  vegetable  oils  almost  100  per  cent.  Bacon  varies  greatly  in  regard  to  the 
amount  of  fat  it  contains;  it  averages  about  92  per  cent.  An  enormous  calory 
value  may  be  obtained  in  the  following  foods:  100  grams  of  Holland  cheese 
(30  per  cent,  fat)  gives  270  calories,  without  including  the  albumin;  100 
grams  of  good  butter,  720  calories.  Fat  and  butter  may  be  mixed  with  vege- 
tables so  as  to  make  them  contain  10  per  cent.,  even  15  per  cent,  of  fat;  bacon 
and  oil  in  salad,  up  to  20  per  cent,  to  40  per  cent. 

Cheese  may  be  pulverized  and  added  to  soups  and  sauces,  and  also  may 
be  made  into  cheese  cakes,  cheese  puddings,  etc. 

Cream  contains  25  per  cent,  of  fat,  and  is,  therefore,  very  valuable;  the 
slight  amount  of  sugar  it  contains  (3  per  cent,  milk-sugar)  need  scarcely  be 
regarded.  Some  cream  contains  even  more  fat  than  this  (up  to  40  per 
cent.).  If  it  is  dairied  in  a  very  cleanly  manner,  it  is  at  first  very  grate- 
ful to  the  taste,  but  after  prolonged  administration  patients  often  do  not 
like  it. 

Milk  is  in  general  use,  and,  even  in  the  most  severe  cases,  of  great  value. 
But  it  must  not  be  supposed  that  the  milk-sugar  is  "  harmless  "  to  the  dia- 
betic, for  it  is  not  much  less  so  than  dextrose  and  cane  sugar;  but  milk  con- 
tains very  little  sugar,  only  about  3  per  cent.  Its  carbohydrate  contents  must 
be  reckoned,  but  it  also  contains  4  per  cent,  to  5  per  cent,  of  fat.  There  are 
several  manufactured  preparations  of  milk  which  contain  a  larger  amount  of 
fat,  and  in  which  the  sugar  is  decreased;  there  are  even  artificial  milks  free 
from  sugar — but  my  patients  soon  become  tired  of  these  preparations. 

Other  fluids  are  to  be  estimated  according  to  their  carbohydrate  value; 
among  wines  only  the  southern  wines  and  champagne  contain  more  than  3  per 
cent.;  these  contain  12  per  cent.  In  beer  the  carbohydrate  value  is  rarely 
under  6  per  cent.  Beer  is  more  harmful  than  this  percentage  would  lead  us 
to  suppose,  as  it  contains  the  greater  part  of  its  carbohydrates  as  maltose; 
this  at  once  decomposes  in  the  intestines  into  dextrose,  and,  for  this  reason, 
the  diabetic  ingests  in  beer  the  most  dangerous,  most  readily  absorbable  form 
of  carbohydrate  food. 

Among  alcoholic  liquors  only  rum,  cognac,  whiskey,  etc.,  are  to  be  con- 


PRACTICAL  THERAPY  101 

sidered  !  Xo  liqueurs  !  These,  and  often  the  so-called  "  bitters,"  contain  enor- 
mous quantities  of  sugar. 

Coffee  and  tea  may  be  looked  upon  as  harmless  for  the  diabetic.  Cocoa 
contains  (without  admixture)  15  per  cent,  of  starch,  and  must  be  estimated 
accordingly. 

If  it  is  desirable  to  increase  the  menu  still  further,  manufacturing  chem- 
ists have  placed  many  preparations  on  the  market  for  the  diabetic.  The  physi- 
cian should  assist  the  diabetic  to  make  his  life  as  comfortable  as  possible, 
yet  the  medical  adviser  must  never  allow  the  reins  to  be  taken  out  of  his 
hands;  unfortunately,  this  often  occurs. 

Which  diabetics  are  to  be  treated  at  a  hospital  (of  course,  one  well  appointed 
with  reference  to  diabetic  treatment),  which  may  be  treated  at  home,  and 
which  should  be  sent  to  Carlsbad,  Vichy,  Xeuenahr,  etc.? 

The  very  mild  cases,  in  which  only  sugar,  potatoes  and  beer  must  be 
restricted  in  order  to  make  the  urine  free  from  sugar,  do  not  need  hospital 
treatment,  though  it  is  advisable  for  them  to  undergo  each  year,  or  at  least 
from  time  to  time,  a  course  of  treatment  at  any  one  of  the  previously  men- 
tioned bath  cures.  Frequently  these  cases  occur  in  elderly  persons,  in  whom 
a  cure  of  this  sort  is  indicated  on  account  of  complicating  arteriosclerosis, 
disease  of  the  liver,  or  gout. 

It  is  often  wise  in  such  cases,  after  sugar  has  been  discovered,  to  send 
them  at  once  to  Carlsbad;  they  return  free  from  sugar,  and  with  a  greater 
docility  and  willingness  to  carry  out  further  dietetic  treatment. 

If  the  case  is  severe,  so  that  it  is  necessary  to  reduce  to  a  minimum  the 
allowance  of  bread  in  order  to  free  the  urine  from  sugar,  the  question  whether 
tin-  patient  should  be  treated  at  home  or  in  a  hospital  must  be  settled  by  the 
individual  circumstances.  If  the  patient  is  sensible,  reliable,  and  in  easy 
circumstances,  treatment  at  home  should  be  tried,  hut  we  must  1 1 < » t  be  too 
optimistic  as  to  results;  as  soon  as  signs  of  unreliability  on  the  patient's  part 
are  detected,  hospital  treatment  should  he  urged.  If.  under  treatment  at 
home,  the  BUgar  has  beeu  considerably  reduced  (to  about  20-30  grams  a  day), 
we  may  smd  the  patient  to  Carlsbad,  whence  lie  often  returns  sugar-free,  and 
he  may  then  more  easily  than  before  be  kept  aglycosuric;  but  this  applies  only 
to  the  mild  cases. 

Every  diabetic  whose  case  is  not  very  mild,  or  who  is  not  reliable  or  well- 
to-do,  as  well  as  every  moderately  -evere  and  every  severe  case  (that  i-,  every 
patient  from  whose  diet  carbohydrates  must  be  largely  or  wholly  eliminated, 
if  only  for  a  time),  must,  to  begin  with,  haw  hospital  treatment.  In  a  hos- 
pital  we  lind   out  how   much   ean   be  attained,  and   we  determine  the  diet  on 

which  the  patient  will  become  Bugar-free,  or  will  have,  at  lea>t.  only  a  gly- 
cosuria of  definite  and  known  intensity.  After  this  he  musi  remain  under 
supervision,  ami  if  the  glycosuria  again  -how-  a  progressive  tendency  he  should 
return  to  the  hospital.  Poor  patient-  with  Bevere  diabetes  need  hospital  treat- 
ment at  leasl  every  year,  of  -i\  or  eight  week-'  duration  the  lir-t  year,  and 
reduced,  if  Deces8ary,  to  four  week-  the  next  year. 

In  the  author'-  experience,  "  hath  cure- "  rarely  henctit  these  patients,  and 
often  do  harm. 


102  DIABETES  MELLITUS 


DISTURBANCES   AND   DANGERS   OCCURRING   IN  THE   DIETETIC 
TREATMENT   OF   DIABETES 

That  disturbances  of  digestion  often  occur  during  dietetic  treatment  has 
been  known  ever  since  the  disease  has  been  treated  by  a  restriction  of  food. 
The  more  violent  disturbances,  such  as  used  to  occur  when  our  knowledge 
was  less,  for  instance,  diarrhea,  sometimes  combined  with  vomiting,  should 
now  be  prevented  entirely.  They  may  be  avoided  in  trustworthy  patients  if 
the  whole  amount  of  food  ingested  is  quantitatively  determined,  if  too  large 
a  portion  of  meat  is  not  allowed,  and  if  we  bear  in  mind  the  sensitiveness  of 
the  patient  as  regards  fat  and  fatty  foods.  Some  patients  lose  their  appetite 
from  the  beginning,  or  as  soon  as  carbohydrate  food,  especially  bread,  is  re- 
stricted. This  anorexia  may  be  avoided  by  giving  them  fruits.  If  the  patient 
likes  the  fruits  prepared  for  diabetics  he  is  very  fortunate;  otherwise  cooked 
or  uncooked  fruits  that  contain  but  little  sugar  may  be  used.  I  am  loath  to 
forbid  fruits  altogether,  and  even  in  the  severe  cases  I  usually  allow  as  much 
as  100  to  200  grams.  Milk,  also,  is  very  valuable ;  ^  to  1  liter  of  milk  a  day 
with  a  restricted  fat-albumin  diet  often  helps  the  patient  over  the  period  of 
anorexia  without  increasing  the  glycosuria  to  any  extent,  and  without  mak- 
ing the  patient  lose  weight.  With  these  precautions,  we  are  not  compelled  to 
break  off  the  dietetic  treatment  as  soon  as  it  is  begun,  but  may  go  on  with  it 
cautiously  as  soon  as  the  appetite  has  improved. 

Every  disturbance  of  appetite,  however,  must  be  seriously  considered,  for, 
on  the  whole,  cases  with  anorexia  are  the  most  difficult  to  deal  with.  In  some 
of  these  cases,  psychic  depression  plays  a  certain  part,  and  if  their  disease  is 
not  too  pronounced,  they  often  get  along  much  better  at  Carlsbad  or  Neuenahr 
than  if  they  stay  at  home,  or  go  to  a  hospital. 

In  acidosis  we  have  an  especially  formidable  hindrance  to  strict  dietetic 
treatment.  In  many  of  the  moderately  severe  cases  it  appears  as  soon  as  the 
diet  is  restricted,  or,  if  already  present,  it  becomes  more  marked  when  the 
carbohydrates  are  limited.  Then  the  patient  is  at  once  in  danger,  because 
acidosis  may  lead  to  coma.  Formerly,  this  often  happened  when  the  diet  was 
restricted  too  suddenly,  and  even  to-day  cases  with  acidosis  are  always  in 
danger  if  severe  gastric  disturbances  occur.  In  the  absence  of  gastric  irritabil- 
ity this  danger  may  be  averted  by  the  administration  of  sodium  bicarbonate. 
'Enough  should  be  given  to  make  the  urine  feebly  alkaline,  and  50  or  more 
grams  in  twenty-four  hours  may  be  necessary.  With  this  precaution  we  may 
endeavor  to  reduce  glycosuria  by  strict  diet  even  where  decided  acidosis  already 
exists.  Of  course  all  food  and  its  calory  value  must  be  determined  with  quan- 
titative exactness,  for,  to  repeat,  it  is  the  disproportion  between  the  quantity 
of  the  products  prepared  in  metabolism  for  oxidation  and  the  power  of  oxida- 
tion itself  which  finds  its  expression  in  acidosis.  In  cases  with  acidosis  we 
must  not  think  of  withdrawing  carbohydrates  entirely,  but  should  allow  60  to 
80  grams  of  bread,  ^  a  liter  of  milk,  and  as  much  as  200  grams  of  fruit.  The 
latter  is  here  particularly  important  in  order  to  prevent  indigestion. 

We  may  count  with  certainty  on  the  fact  that  if  the  acetone  reaction  be- 
comes marked  at  the  onset,  the  cause  is  simply  the  urinary  sodium,  that  is,  the 


TABLES 


103 


alkalinity  of  the  urine.  Sometimes  the  diacetic  acid  (ferric  chloric!)  reaction 
also  becomes  marked:  but  this  should  not  be  allowed  to  occur  after  the  first 
few  days.  In  case  the  reaction  becomes  still  more  intense,  so  that  the  urine 
blackens  on  the  addition  of  ferric  chlorid,  milk  should  be  cautiously  added  to 
the  diet,  and  its  calory  value  subtracted  from  that  of  the  meat,  which  should 
be  correspondingly  reduced.  Otherwise,  if  the  general  condition  of  the 
patient  remains  good,  we  may  maintain  an  expectant  attitude  until  the  ferric 
chlorid  reaction  becomes  less  marked,  which  usually  occurs  in  eight  to  four- 
teen days,  sometimes  earlier  or  later.  When  this  diminution  of  acidosis  begins 
the  danger  from  this  source  is  over;  acidosis  gradually  disappears  and  will 
not  cause  trouble,  even  should  a  further  restriction  of  the  carbohydrates  be 
necessary. 

Of  course,  if  symptoms  of  coma  appear  we  must  increase  the  dose  of  sodium 
bicarbonate  until  the  urine  is  alkaline.  Sometimes  100  grams  or  more  of 
sodium  bicarbonate  must  be  given  in  twenty-four  hours.  In  almost  every  case 
of  this  kind,  it  is  milk  which  answers  our  purpose  best. 

VI.    TABLES 


Tables  of  foods:  different  kinds  of  meat,  fish,  eggs,  sausages,  meat-preserves,  and 
various  kinds  of  cheese,  arranged  according  to  the  amount  of  fat  they  contain. — Fat, 
butter  and  varieties  of  milk,  with  percentages  of  fat  and  carbohydrates. — Bread,  flour 
and  vegetables,  with  percentages  of  carbohydrates. — Fruits  and  their  carbohydrate 
(sugar  +  pectin)  contents. — Beer,  wine  and  spirits,  with  their  amounts  of  alcohol  and 
carbohydrates. — Plan  for  calculating  the  food-value  of  the  diet  in  calories. — Short 
popular  dietary  instructions  for  diabetics. 

MEAT   WITH   PERCENTAGE  OF   FAT 


Percentage 
Of  Fat. 

1.  Fat  pork 37.34 

8.  Very  Cat  mutton 36.39 

B,  River  eel 28.37 

4.  Pal  beef  (from  ox) 26.38 

5.  River  Lamprey  (smoked  or  pickled)  25.59 

6.  Salt  herring." 16.89 

7.  Sprat 16.94 

8.  v ery  f al  horseflesh 16.64 

9.  Salt  mackerel 14.10 

10.  Salmon  (smoked  or  salted) 11.86 

11.  Mackerel  (fresh) 10.10 

12.  Rabbil  (futi 9.76 

18.  Chi.-k. mi  (fan 9.84 

14.  Bloater 8.61 

15.  Bleak 8.13 

16.  Pal  cow's  meat 7. 7<» 

17.  Pal    \eal 7.41 

18.  Presh  herring 7.11 

lit.  Swedish  anchovy  (salt) 7.06 

•J<>.  Lean  pork ". 6.81 

81.  Salmon 6.42 

88.  Swedish  anchovy  (fresh) 5.87 

88.  Half  r.ii  mutton. 5.77 

84  Medium  fal  beef  (ox) 5. 19 

86.  Sea  eel 5.02 

88.  Duok  (wild) 8.11 


27. 
28. 
29. 
30. 
31. 
32. 
33. 
34. 
35. 
36. 
87. 
88. 
89. 

in. 
41. 

12. 

18. 

II. 

15. 

I».. 

17. 

18. 

19. 

50. 

51. 


Percentage 
of  Fat. 

Groundling 2.68 

55 
21 
92 

Ni 

7* 
77 
60 


Medium  fal  horseflesh 2 

Anchovy 2 

Roe  (deer) 1 

Plaice 0.25-1 

Lean  cow's  meat 1 

Fieldfare 1 

Lean  beef  (ox) l 

Partridge 1 .43 

Chicken  (lean) 1.42 

Hare 1.18 

Carp 1.0!> 

Pigeon 1.00 


Veal  dean) 

Stock-fish  

( tadua 

Pike 

Very  lean  horseflesh  (minimum). 

Roach 

Perch 

Codfish 

<  tystere 

<  'lab 

I [addock 

Torek 


88 
.78 
.70 
.51 
.50 
.17 
.44 
.89 
.37 

.80 

.80 


104 


DIABETES  MELLITUS 


EGGS 


Percentage 
of  Fat. 

1.  Hens'    eggs    (average    weight,    53 

grams) 12.11 

2.  Duck  ejnrs 15.49 


Percentage 
of  Fat. 

3.  Lapwing  eggs 11.66 

4.  Carp  roe 6 .  00 

5.  Caviar 15 . 70 


SAUSAGES  AND   PRESERVED   MEATS 


Percentage 
of  Fat. 

1.  Clean,  well-smoked,  meat-free  bacon  92.20 

2.  Westphalia  sausage 39.88 

3.  Cervelat  sausage 39 .  76 

4.  Frankfurters 39.61 

5.  Westphalia  ham 36 .  48 

6.  Smoked  beef-tonjrue 31 .61 


Percentage 
of  Fat. 

7.  Pomerania  goose-breast 31 .49 

8.  Smoked  beef 15.35 

9.  Tinned  meat 12.63 

10.  Blood-sausage 1 1 .  48 

11.  Hard  smoked  sausage 11.40 

12.  Dried  beef 5.24 


CI  I EESE 


Percentage 
of  Fat. 

1.  Neufchätel 40.80 

2.  Stilton  cheese 34 .  55 

3.  Stracchino  cheese. 33.67 

4.  Roquefort  cheese 33.44 

5.  Brick  cheese 32.78 

6.  Cheddar  cheese 32.37 

7.  Edam  cheese 30.26 

8.  Gervais  cheese 29.75 

9.  Emmenthal  cheese 29.67 

10.  Gloucester  cheese 28.08 

11.  Gruyere  cheese 28.04 


Percentage 
of  Fat. 

12.  Cheshire  cheese 27.46 

13.  Holland  cheese 26.70 

14.  Artificial  oleomargarin 25.95 

15.  Swiss  cheese  (ordinary) 23.54 

16.  Artificial  fat  cheese 21.70 

17.  Romadour 20.66 

18.  Camembert 21 .00 

19.  Brie 20.27 

20.  Parmesan  cheese ...  19.52 

21.  Swiss  caraway  cheese 12.11 

22.  Meager  cheese  6 .  84 


DIFFERENT  FATTY   FOODS   AND  VARIETIES   OF   MILK 

(Arranged   according    to   their  fat  and  carbohydrate — sugar — contents.) 


Fat.  Carbohy. 

1.  Plant-oil 100.00 

2.  Bone-marrow 100.00     

3.  Artificial  butter 87.76     

4.  Butter 83.27  0.8-0.58 

5.  Lard 100.00  ....... 

6.  Cream 26.75  3.52 

7.  Condensed  cow's    milk 

without    addition  of 

cane-sugar 13.19  15.38 


Fat.  Carbohy. 

8.  Sheep's  milk 6.83  4.73 

9.  Goat's  milk 3.94  4.39 

10.  Cow's  milk 3.65  4.81 

11.  Ass's  milk 1.64  5.99 

12.  Buttermilk 93  3.73 

13.  Kumiss     from      cow's 

milk 85  3.10 

14.  Skimmed  milk 74  4.75 

15.  Whey 23  4.70 


The  liver  of  fattened  geese  (Strassburg  liver)  should  by  no  means  be  excluded  from 
the  diet  on  account  of  its  supposedly  high  percentage  of  glycogen,  for,  in  fact,  this  is 
slight,  and  does  not  amount  to  more  than  from  0.96  per  cent,  to  2.8  per  cent,  (of  the 
fresh  liver).  I  am  unable  to  find  any  quantitative  reports  of  the  percentage  of  fat  in 
these  livers,  but  it  may  safely  be  assumed  to  be  about  30  per  cent. 


BREAD,  FLOUR  AND  VEGETABLES 

(According  to  their  percentage  of  carbohydrates.) 


Per  cent. 

1.  Fine  flours  (arrowroot,  sago,  maize, 

etc.) 83.31 

2.  Potato  flour  80.83 

3.  Biscuit  flour  for  children 77.30 

4.  Noodles 76.77 

5.  Rice 76.52 


Per  cent. 

6.  Oatmeal 75.95 

7.  Cakes 73.30 

8.  Wheat  rusks 72.00 

9.  Wheat  for  rolls 72.00 

10.  Barlev  flour 71.74 

11.  Rye  flour 69.66 


TABLES 


105 


BEE  AD,    FLOUR   AND   VEGETABLES    {continued) 
Per  cent. 


12.  Barley  bread 69.06 

13.  Coarse  wheat  flour,  including  bran 

for  Graham  bread 65 .00 

14.  Oatmeal  gruel 64.73 

15.  Oat  bread 64.21 

16.  Leguminose ...  64.05 

17.  Rolls 63.00 

18.  Coarse  wheat  bread 53.00 

1!).   live  bread 49.25 

80.  Soldiers'  bread 49.00 

21.  Pumpernickel 47.00 

22.  So-called  Graham  bread 39.00 

33.  Aleuronal  bread  (Strassburg make)  34.30 
84  Aleuronat  bread  (after  Ebstein)...  27.50 
25.  Peas  (dry) 52.36 

86.  Beans  (dry) 49.01 

27.  Lentils  (dry) 53.46 

88.  Bishop's-eap 43.31 

89.  Truffles  (air  dry) 37.40 

30.   Soja  beans....."    .   29.99 

81.  Mushrooms  (air  dry) 28.99 

82.  Garlic ' 26.31 

33.  Onions  (white) 25.69 

34  Potatoes 20.69 

35.   Horseradish    15.89 

B8.  Black  salsify1 15.00 

87.  Sweet  potato  (topinambur) 14.00 

38.  Green  garden  peas 12.00 

89.  Celery 11.80 

40.  Sugar  beets 11.72 

41.  Green  cabbage 1 1 .  63 

42.  Pepperworl 11.61 

18.   Pale  red  onions  (the  tuber) 10.88 

44  Truffles  (fresh) 10.73 

45.  Red  beets 9.56 


Per 


46.  Other-wort 

47.  Carrots  (large) 

48.  Beet-root 

49.  Scallion 

50.  Radish 

51.  Kohlrabi,  underground  (tuber). 

52.  Carrots  (small) 

53.  Parsley 

54  Dill 

55.  Green  horse  beans 

56.  Pumpkin 

57.  Turnip  leaves 

58.  Watermelon 

59.  French  beans ' 

60.  Leek  (bulb  and  root) 

61.  Red  cabbage 

62.  Brussels  sprouts 

63.  Cabbage  (Savoy) 

64.  Kohlrabi '. 

65.  White  cabbage 

66.  Cauliflower 

67.  Leek  (leaves) 

68.  Spinach  

69.  "  Sugar  loaf  " 

70.  Tomato 

71.  Radish  (small) 

72.  Roman  salad  (lettuce) , 

73.  Sorrel 

74.  .Mushrooms  (fresh) 

Prickly  lettuce 

Asparagus 

Endive 

Cucumbers 


75. 


78. 


cent. 
9.46 
9.35 
9.26 
9.08 
8.43 
8.18 
8.18 
7.44 
7.43 
7.35 
7.33 
7.28 
7.14 
6.60 
6.53 
6.25 
6.22 
6.02 
4.00 
4.87 
4.55 
4.55 
4.44 
4.29 
4.07 
3.79 
3.55 
3.43 
2.91 
2.73 
2.63 
2.58 

9  98 


79.  Headed  lettuce 2.19 


PERCENTAGE   OF  CARBOHYDRATES  IN  DIFFERENT   FRUITS,  ETC. 
(Sum  of  sugar  and  imn-nifrogenous  [sugar-producing]  extracts  [pectin].) 

Sugar. 

r,a,ps-  ••••'fSuga 


Dextrin. 

ar.  .  . 


2.  Locust-bean. 


3.4     ) 
58.00 f 


r»  •  i  (  Cane-sugar 

Dned  prunes j  Grape-sSgai 


0.22  ) 
44.19  \ 


Raisins 54.56 

Dried  apples 48.88 

Dried  figs 49.79 

Driedpears <  Grape-sugar    84.14 

1  |  ( ane-sugar       4.9!» 

I  >rie,l  cherries 81.22 

Bananas 

Chestnuts  (genuine) 

Sunflower  seed 

Poppy  s 1 

Winegrapes. ..   .   14.86 

>  Ripe  black  salsify  and  sweel  potato  (topinambur)  contain  levulose  almost  exclu- 
sively. The  unripe  roots  contain  much  dextrose,  the  proportion  between  levulose  and 
dextrose  in  both  i>  inconstant  and  variable,  as  the  roots  are  not  always  quite  ripe.  In 
French  beans  (59),  the  substance  given  as  being  a  carbohydrate  is  inosite,  which  is  not 

a  genuine  carbohydrate,  and   is  entirely   harmless. 


ee  extracts. 

Total. 

13.00 

74.40 

67.67 

67.67 

17.69 

62.10 

7.48 

63.04 

11.40 

54.23 

49.7!» 

19.84 

48.47 

14.19 

46.51 

88.06 

23.(»5 

88.84 

88  84 

80.08 

80  08 

i-  ;  i 

IN. 74 

1.98 

16.82 

106 


DIABETES  MELLITUS 


PERCENTAGE   OF    CARBOHYDRATES    IN    DIFFERENT   FRUITS    (continued) 

Sugar.  N.-free  extracts.        Total. 

14.  Green  gages 3.16  11.46  14.62 

15.  Mirabelle  plums 3.97  10.07  14.14 

16.  Apples 7.22  5.8*1  13.03 

17.  Cherries 10.24  1.76  12.00 

18.  Mulberries 9.19  2.03  11.22 

19.  Pears 8.26  3.54  11.80 

20.  Peaches 4.48  7.17  11.65 

21.  Prunes 6.15  4.02  11.07 

22.  Apricots 4.69  6.35  11.04 

23.  Hazelnuts 9.03  9.03 

24.  Gooseberries 7.03  1.40  8.43 

25.  Plums 3.56  4.68  8.24 

26.  Cocoanut 8.06  8.06 

27.  Walnuts 7.89  7.89 

28.  Currants 6.38  0.90  7.28 

29.  Almonds 7.23  7.23 

30.  Strawberries 6.28  0.48  6.76 

31.  Whortleberries 5.02  0.87  5.89 

32.  Candlenuts  (bankulnut) 5.88  5.88 

33.  Blackberries 4.14  1.44  5.88 

34.  O ran ses. 4.59  0.95  5.54 

35.  Raspberries 3.86  1.44  5.30 

36.  Peanuts 1.85  1.85 

37.  Cranberries 1.53                1.53 

DIFFERENT   KINDS  OF  BEER 

{According  to  their  alcohol  and  carbohydrate  contents.) 

Carbo-  Alcohol, 
hydrates.         vol.  per  cent. 

1.  Braunschweiger   Mumme 52.29  2.96 

2.  Wheat  beer  from  Celle 10.45  0.70 

3.  Porter 7.55  5.35 

4.  Bock  beer  (Märzen,  Saloon,  double  beer,  etc.) 7.20  4.74 

5.  Rice  beer 6.83  4.02 

6.  Export  beer 6.48  4.31 

7.  Ale 6.03  4.89 

8.  Lager  or  summer  beer 5.78  3.95 

9.  Swedish  beer 5.68  3.89 

10.  English  beer 5.65  5.55 

11.  Lighter  beer  varieties  (usual  yeast  and  winter  beers) 5.49  3.46 

12.  Berlin  weiss  beer  (1878) 4.28  3.33 

13.  Belgian  beer 3.84  6.08 


PERCENTAGE    OF    CARBOHYDRATES    (SUGAR  -f-  "EXTRACT")    IN    WINES 

AND   SPIRITS  Alcohol, 

vol.  per  cent. 

1.  Russian  Dorvy-vodka 62.00 

2.  Arrack 60.05 

3.  American   whiskey 60 .  00 

4.  French  cognac 55 .  00 

5.  Rum 51 .40 

6.  English  whiskey 49.40 

7.  Ordinary  brandy  (s.  schnaps) 45 . 00 

8.  Sherry.*. 20.89 

9.  Port  .' 20.00 

10.  Madeira 19.20 

11.  Swedish  punch 18.90 

12.  Muscatel 16.05 

13.  Greek  wine 15.40  \  5J?X" 

(Mm, 

14.  Tokay 14.89 

15.  Rüster  Ausbruch 14.72 


Carbohydrates 
(sugar  +  "extract"). 

6'.8* 


3.53 

6.99 

5.28 

33.20 

18.60 

41.00 

2.65 

72.4 


TABLES 


107 


99 

804 

4 

o 

2 

0 


PERCENTAGE    OF    CARBOHYDRATES    IX    WINES    AND    SPIRITS    (C0nti?llied) 

Alcohol.  Carbohydrates 

vol.  per  cent,      (sugar  +  "extract"). 

10.  Malaga L4.22  17.27 

17.  Italian  wine 13.86  3.63 

is.  Tyrolesewine 12.57  3.67 

19.  Bohemian  white  wine 12.09 

20.  Moselle  and  Saar  wine 12.06 

21.  Palatinate  wine 11.55 

22.  Rhine  wine 11.45 

2:>.  Bohemian  red  wine 11.16 

24.   Rhine-Hessian  white  wine 1 1  .07 

2.').  Baden  wine 11.07  1.7 

26.  French  champagne 10.35  16.7 

27.  French  wine 10.34  2.0 

28.  French  white  wine 10.30  1 

29.  A Natian  wine    10.14  1 

30.  Rheingau  wine  (red  wine) 11.08  3 

31.  Alsatian  line  wine 9.938  1 

82.   Aar  wine 9.90  2 

88.  Hungarian  wine 9.78  2. 

:J4.  Hessian  wine 9.67  1.2 

86.  Vorarlberg  wine 9.66  1.4 

B6.Swisswine 9.56  1.972 

:;7.  Red  Rhine  wine 9.55  3.06 

38.  Austrian  rod  wine 9.49  2.7 

89.  Rhine  wine  mousseux 9.44  10.70 

40.  French  red  wine 9.40  2.3 

41.  Württemberg  wine 7.85  2.2 

42.  Fruit  wine 4.28-5.65  2 .75-4.75 


.9 
.7 
.0 
.8 
.5 
.  265 


FOR  CALCULATING    THE  NUTRITION   AND  CALORY  VALUE  OF   THE   DIET 


Food. 

Ai.i'.r.MlN. 

Fat. 

Carboh. 

Calories. 

Amount. 

Per  cent. 

Amount 

Per  cent. 

Amount. 

Per  cent. 

Amount. 

Per  cent. 

Amount. 

1.    Meat 

22.0 
1 .-, .  g 
6.0 
3.1 
7.5 
6.25 
22.0 
25.0 
28.1 
0.63 
0.63 

4.0 
48.0 
5.5 
3.0 
1.0 

|S. II 

30.0 

8.0 

0.10 

8-20 

87.00 

100.00 

100.00 

Gran 

1.5 
65. 

1.3 

0.85 

s. 

125. 
500. 

75. 

59. 
295. 
250. 
(127. 
375. 
150. 

80  200 

800. 

1 

900. 

700. 
<  Saloriet 

2.  Sausage 

B.  Eggs,  each 

1.  Milk 

6.  Rolls 

(i.  Wheat  bread 

7.  D-st  icka  (Rademann).. . 

it.    (    heese,    lean 

10.  B  luillon 

1 1.  Vegel  ahles 

18.  Butter 

18.  Lard    

14  Oil 

L5.  Alcohol   (per  cent,   in  i 
Pal 

Albumin 

T.Mai 

Subtraction  for  ezcrel  ion  of 

agar 

Total 

Net  calory  vah f  f 1  per 

kilogn 

in  body-weicrht .  . 

108  DIABETES  MELLITUS 


SHORT   POPULAR  DIETETIC  RULES   FOR   DIABETICS 

No  food  is  to  be  given  to  a  diabetic  in  unrestricted  amount!  The  follow- 
ing rules  are  not,  therefore,  to  be  understood  as  permitting  any  food  in  indis- 
criminate quantity.  The  physician  must  decide  in  the  beginning  how  much 
of  each  food  may  be  eaten,  and  the  patient  must  comply  with  his  orders. 
These  tables  are,  therefore,  subject  to  variation. 

1.  Meats:  bouillon  or  meat  broth;  meat  of  any  kind,  stewed,  grilled, 
smoked  or  preserved.  The  addition  of  flour  or  bread  in  the  preparation  of 
meat  is  to  be  avoided;  hence,  Wiener  schnitzel,  stuffing  of  meat,  stuffing  of 
chicken,  etc.,  are  forbidden. 

The  kind  of  meat  is  of  little  importance  except  for  the  amount  of  fat  it 
contains;  the  patient  may  take  beef,  pork,  mutton,  veal,  goat,  game,  venison, 
birds,  etc.  The  part  of  the  body  used  for  food  is  also  of  little  account ;  muscle, 
kidney,  pancreas,  brain,  giblets,  are  all  allowed.  On  account  of  the  glycogen 
it  contains,  liver  forms  an  exception  and  is  forbidden. 

Flour  and  bread  should  not  be  used  in  the  preparation  of  sauces. 

2.  Fish  of  any  kind  are  allowed.  Still,  as  they  do  not  contain  the  same 
percentage  of  fat,  they  are  of  different  values.  The  fattest  are  the  eel,  river 
lamprey  and  herring;  most  others  are  lean.  Lobster  and  crab  have  the  same 
value  as  lean  fish.  The  same  rules  apply  to  their  preparation  as  to  that  of 
meat.  Shell-fish,  oysters  and  snails  are  not  advisable  on  account  of  their 
high  percentage  of  glycogen. 

3.  Eggs  and  fat- foods.  Eggs  of  any  kind  and  preparation  (without  flour) 
are  allowed;  also  good  sausage  (except  liver  sausage),  ham,  bacon,  caviar, 
Strassburg  goose-liver,  sardines,  fat,  cheese,  butter,  oil,  etc. 

4.  Milk  preparations.  Small  quantities  of  not  too  sweet  cream  are  allowed, 
also  sour  milk  from  which  the  milk-sugar  has  at  least  partially  disappeared 
through  fermentation.  Regarding  milk,  special  orders  from  the  physician 
must  be  obtained. 

5.  Vegetables  and  starchy  foods.  Of  vegetables  we  allow  spinach,  cauli- 
flower, French  beans,  asparagus,  lettuce,  cucumbers,  small  quantities  of  celery 
and  of  crisp  cabbage,  mushrooms  and  other  edible  fungi  (except  truffles) 
and  sauerkraut,  as  much  fermented  and  as  old  as  possible. 

Prohibited  are  flour,  rice,  cereals,  sago,  tapioca,  potatoes,  peas,  lentils, 
dried  beans,  green  peas,  yellow,  white  and  red  beets,  horseradish,  arrow-root, 
and  corn-starch. 

The  orders  of  the  physician  must  be  strictly  followed  as  to  the  amount  of 
bread  to  be  taken  in  twenty-four  hours. 

Gluten  bread,  Graham  bread,  aleuronat  bread,  which  are  recommended  as 
substitutes  for  ordinary  wheat  and  rye  bread,  are,  on  account  of  the  larger  or 
smaller  amount  of  flour  they  contain,  to  be  used  only  after  consulting  the 
physician. 

6.  Fruits,  etc.  Advisable  are  mandarins,  oranges,  currants,  raspberries, 
gooseberries  and  strawberries,  but  especially  cranberries;  also  nuts  and 
almonds. 

7.  Beverages:  Allowed  are  water,   mineral   water,   coffee,   tea,   red  wine 


TABLES  109 

which  is  not  too  sweet,  or  white  wine,  cognac,  cherry  brandy,  and  pure  rye 
whiskey. 

Prohibited  are  cocoa,  chocolate,  sweet  wine,  champagne,  and  also  beer 
and  liqueurs. 

8.  Spices.  Pepper,  also  red  pepper,  and  small  quantities  of  English  mus- 
tard are  harmless. 

Saccharin  or  crystallose  is  allowed  in  small  quantities  (0.1  gram  per 
diem)  to  sweeten  the  food. 

Sugar,  also  levulose,  is  forbidden  in  any  form,  as  well  as  honey. 

Every  diabetic  should  be  advised  to  eat  as  much  fat  and  butter  as  he  can 
without  disturbing  the  appetite;  hence,  fat  gravies,  fat  meat,  vegetables,  and 
salads  prepared  with  considerable  oil  are  recommended. 


DIABETES   INSIPIDUS 
Bv  D.   GERHARDT,   Strassburg 

Diabetes  insipidus  belongs  to  those  diseases  which  are  of  great  interest 
to  physicians,  less  because  of  the  frequency  of  their  occurrence  than  on  account 
of  the  peculiarities  of  the  pathological  disturbances,  and  their  definite  analogy 
to  physiological  experiment. 

Strictly  speaking  the  disease  has  but  one  symptom:  decided  increase  in 
the  excretion  of  urine.  Everything  else  that  is  mentioned  among  the  symp- 
toms is  either  a  consequence  of  this  disturbance  or  is  only  an  inconstant  accom- 
panying symptom. 

Increase  of  the  excretion  of  urine  occurs  in  quite  a  number  of  pathological 
conditions  as  a  more  or  less  regular  symptom;  thus,  particularly  in  contracted 
kidney,  in  the  convalescence  of  febrile  diseases,  and  during  the  absorption  of 
fluids  from  the  cellular  tissues  or  serous  cavities.  But  we  speak  of  diabetes 
insipidus  only  when  none  of  these  conditions  is  present. 

This  rare  disease  occurs  at  all  ages,  most  frequently  between  the  tenth 
and  fortieth  years  of  life.  The  male  sex  is  about  twice  as  frequently  affected 
as  the  female. 

There  are  great  variations  in  the  severity  of  the  clinical  picture  in  differ- 
ent cases.  In  many  persons  the  disease  lasts  for  decades,  and  even  for  a  life- 
time; and  beyond  the  inconvenience  of  frequent  urination  and  the  corre- 
sponding thirst,  there  are  no  disturbances  of  the  general  health.  In  others 
nutrition  suffers  greatly,  and  there  is  a  lessening  in  the  capacity  for  work 
yet  without  any  influence  on  the  duration  of  life.  In  still  other  cases  it  is  a 
severe  disease  which  soon  terminates  in  death. 

This  great  difference  in  the  severity  of  the  symptoms  makes  it  likely  that 
there  is  no  single  disease  corresponding  to  the  name  "  diabetes  insipidus," 
but  that  a  number  of  different  diseases  in  which  the  most  conspicuous  symp- 
tom is  the  profuse  production  of  urine,  are  grouped  under  this  name. 

We  know  that  an  increase  of  urinary  excretion  may  be  artificially  pro- 
duced by  increasing  the  intake  of  fluid,  by  raising  blood-pressure,  by  irritation 
of  certain  areas  of  the  central  nervous  system,  by  direct  irritation  of  the  kid- 
neys with  certain  pharmacological  remedies,  and  finally,  by  the  introduction 
of  so-called  diuretics,  which  in  their  excretion  through  the  kidneys  carry  with 
them  profuse  quantities  of  water. 

It  is  probable  that  in  the  genesis  of  the  clinical  pictures  which  have  been 
included  under  the  name  of  diabetes  insipidus,  several  of  these  factors  and 
110 


DIABETES   INSIPIDUS  111 

perhaps  all  of  them  have  played  a  part,  and  it  is  possible  that  upon  the  basis 
of  such  difference  in  the  manner  of  production  a  separation  of  the  varying 
clinical  pictures  into  individual  groups  may  be  made.  In  such  an  attempt, 
however,  we  can  hope  for  nothing  more  than  partial  success. 

One  group  of  cases  in  which  clinical  observation  or  an  anatomical  rinding 
shows  organic  disease  of  the  brain  can  he  sharply  denned.  Since  Claude  Ber- 
nard's celebrated  experiments  have  shown  that  by  injuring  an  area  in  the 
floor  of  the  fourth  ventricle  (close  to  the  glycogenic  center)  simple  polyuria 
may  he  produced,  many  cases  of  this  type  of  diabetes  insipidus  have  been  col- 
lected, and  it  has  been  determined  that  in  the  majority  of  these  cases  there 
has  been  a  definite  change  in  the  posterior  cerebral  areas,  particularly  in  the 
region  of  the  sinus  rhomboidalis. 

These  cases  are  in  harmony  with  the  teachings  of  physiology;  they  form 
a  well-defined,  genetically  connected  group,  and  though  we  may  be  in  doubt 
whether  certain  cases  belong  in  this  category  or  not.  this  doubl  is  due  to  the 
fact  that  in  these  instances  the  alterations  attributed  to  the  brain  are  indefinite. 

Only  a  small  proportion  of  all  cases  belongs  to  this  group.  Among  the 
remainder,  a  group  may  be  separated  in  which  the  increased  excretion  of 
urine  is  simply  the  result  of  an  increased  ingestion  of  fluid.  In  a  number 
of  cases  it  has  been  found  that  by  limiting  the  ingestion  of  water,  gradually 
or  suddenly,  we  produce  a  short  period  of  discomfort  followed  by  cure  of  the 
disease.  Here  the  obvious  explanation  is  that  the  cause  of  the  trouble  is  sim- 
ply an  increased  ingestion  of  fluid  whether  due  to  an  unexplained  thirst  or 
to  habit;  in  short  that  polydipsia  is  the  trouble. 

Regarding  many  other  cases   it   musl   remain  questionable  whether  they 

.should  be  included  in  this  group,  partly  because  - symptoms  are  opposed 

to  this  idea,  partly  because  the  decisive  test  of  limiting  the  ingestion  of  fluid 
cannot  be  carried  out. 

Still  other  cases  are  proved  by  special  characteristics  in  the  clinical  pic- 
ture to  depend  upon  an  increased  excretion  of  water  by  the  kidneys,  inde- 
pendent of  the  ingestion  of  fluid.  The  facts  which  justify  this  explanation 
are:  First,  a  diminished  excretion  of  water  by  the  4;in  and  lungs  in  spite  of 
the  greal  natural  alllux  of  water  to  these  parts  and.  as  a  more  easily  recognized 
expression  of  this  condition,  an  excessive  amount  of  urine  as  compared  with 
the  amount  of  fluid  ingested  ;  naturally  the  implied  diminution  of  the  amount 
of  water  normally  ingested  is  at  the  expense  of  the  watet-  consumed  with  solid 
food.  Secondly,  we  note  the  independence  of  the  excretion  of  urine  upon  the 
ingestion  of  water,  bo  that,  for  example,  after  a  sudden  stoppage  of  the  intake 
of  fluid,  the  production  of  urine  continue-  unchanged,  at  any  rate  during  the 
nc\t    \'<-\v  hours. 

These  conditions,  polydipsia  and  true  polyuria,  are  in  practice  very  diflfi- 
cult  to  separate,  and,  in  spite  of  much  labor  which  some  authors  have  bestowed 

upon  this  point  during  the  la-t  decades  of  the  preceding  century,  the  sepa- 
ration of  these  forms  has  not  gained  general  acceptance.  So  it  is  with  the 
attempt  made  by  Schapiro  and  other-  to  distinguish  a  form  of  diabetes 
insipidus  <\u<-  to  disease  of  the  abdominal  sympathetu  and  to  characterize  it 
clinically  ;  it  is  not  con\  i n<  i dlt. 


112  DIABETES  INSIPIDUS 

To  gain  a  comprehensive  grasp  of  the  manifold  clinical  phenomena  of  the 
disease,  it  is  still  most  convenient  to  group  the  cases  according  to  their  appar- 
ent etiology.    Thus  the  following  forms  may  be  described : 

1.  Diabetes  insipidus  in  cerebral  diseases, 

2.  Diabetes  insipidus  in  functional  neuroses, 

3.  Diabetes  insipidus,  idiopathic  form. 

Further  description  will  show  that  under  each  of  these  divisions  several 
very  different  clinical  pictures  are  grouped  together. 

SYMPTOMS    AND    CLINICAL    COURSE 

The  essential  symptom  is  the  large  quantity  of  urine.  The  daily  excre- 
tion is  increased  to  5,  10,  even  20  liters,  and  in  the  severest  cases  it  amounts 
to  even  more  than  this;  cases  have  been  reported  in  which  the  weight  of  the 
dailv  quantity  of  urine  was  as  great  as  the  body-weight.  These  cases  occurred 
in  children  weighing  20^  and  27^  pounds;  a  patient  of  Trousseau  voided  43 
liters  daily. 

Of  course  the  urine  is  greatly  diluted,  almost  colorless,  and  feebly  acid; 
its  specific  gravity  is  low,  usually  under  1.010,  and  it  may  even  fall  nearly 
to  that  of  water. 

As  a  rule  the  normal  solids  of  the  urine  show  no  deviation  from  their  ordi- 
nary amounts.  It  is  true  that  the  daily  amounts  of  urea  and  sodium,  chlorid 
have  been  found  abnormally  large  or  abnormally  small  in  a  number  of  cases, 
but  it  is  extremely  probable  that  this  was  in  consequence  of  a  profuse  or  scanty 
ingestion  of  albumin  and  sodium  chlorid  in  the  food ;  diabetes  insipidus  in 
itself  does  not  influence  these  values.  Uric  acid  and  Jcreatinin  are  found  in 
the  usual  amounts;  special  importance  has  been  attached  to  the  occurrence 
of  inosite  in  urine  free  from  sugar;  but  according  to  the  investigations  of 
Strauss  and  Kiilz  it  is  only  the  result  of  profuse  excretion  of  urine  such  as 
may  occur  in  the  healthy  after  abundant  ingestion  of  water. 

The  manner  in  which  the  urine  is  discharged  varies  in  individual  patients; 
in  most,  the  number,  in  others,  only  the  quantity,  of  the  individual  evacua- 
tions is  increased.  Many  patients  excrete  more  urine  during  the  night  than 
during  the  day,  as  in  cases  of  contracted  kidney;  others  do  not  show  this 
peculiarity.  The  "morning  flood  of  urine"  (Quincke),  that  is,  the  produc- 
tion of  a  large  amount  of  urine  as  soon  as  the  patient  wakens  in  the  morning 
even  when  he  stays  in  bed  and  takes  no  fluid,  is  quite  similar  to  what  occurs 
in  the  case  of  healthy  persons.  Further,  as  regards  the  influence  of  increased 
body  warmth,  the  excretion  of  urine  in  diabetes  insipidus  appears  to  conform 
to  the  condition  of  health,  i.  e.,  in  fever  whether  produced  naturally  or  arti- 
ficially (by  injections  of  albumoses)  it  is  decreased. 

In  the  main  the  kidney  functions  more  independently  of  the  ingestion  of 
water  than  in  the  healthy  individual ;  after  the  ingestion  of  a  large  amount 
of  fluid  the  amount  of  urine  does  not  increase  so  rapidly  as  in  health  (though 
even  to  this  peculiarity  there  are  many  exceptions).  After  a  decreased  inges- 
tion of  water  it  is  true  the  urine  decreases,  but  not  so  rapidly  nor  so  markedly 
as  in  health. 


SYMPTOMS   AND  CLINICAL  COURSE  113 

The  kidneys  apparently  endeavor  to  excrete  more  water :  they  withdraw 
fluid  from  the  body  approximately  at  a  uniform  rate;  if  water  is  not  supplied 
in  plentiful  amounts,  inspissation  of  the  blood  occurs  more  readily  than  in 
healthy  individuals.  Thus,  in  a  case  studied  by  Strubell,  in  a  patient  whose 
thirst  was  unrelieved  by  water  for  several  hour-,  tin-  -pecific  gravity  of  the 
blood  rose  from  1.055  to  1.071. 

Similarly  to  the  condition  in  contracted  kidney  (though  here  the  secretion 
of  urine  is  increased  from  other  causes)  we  find  in  cases  of  diabetes  insipidus 
a  diminution  of  the  excretion  of  water  through  the  skin  and  lungs.  We  are 
not  prone  to  attribute  this  condition  to  disturbance  of  the  functions  of  the 
skin  and  lungs  but  are  rather  disposed  to  assume  that  most  of  the  water  has 
Keen  discharged  through  the  kidney-,  and  hence  there  is  not  enough  left  for 
the  -kin  and  the  lungs.  Only  after  the  disease  has  Lasted  a  Long  lime  doe-  tin- 
diminution  in  the  activity  of  the  skin  attain  a  certain  independence  in  the 
clinical  picture,  as  it  doe-  in  nephritis. 

Insensible  perspiration,  as  well  as  sweat  formation,  is  diminished,  and  the 
fact  that  no  sweating  occurs  in  great  summer  heat  has  been  noted  in  a  number 
of  clinical  historic-.  Stoermer  states  that  one  of  his  patients  -bowed  a  rise  in 
temperature  to  102.9°  F.  on  very  hot  day- :  on  account  of  his  inability  to  sweat, 
the  patient  apparently  was  unable  to  cool  his  body  in  opposition  to  the  high 
external  heat. 

Naturally  the  increased  excretion  of  water  also  requires  an  increased  intake 
of  water,  and  accordingly  the  normal  desire  for  water  is  decidedly  increased 
in  all  cases  of  diabetes  insipidus.  Decided  thirst  may  be  the  first  and  most 
troublesome  symptom  of  the  disease,  hut  the  physician  (in  typical  cases) 
in  it  only  a  result  of  Ihr  diabetes.  How  far  a  primary  <ni<!  pathological  thirst 
with  secondary  increase  in  the  amount  of  urine  must  he  assumed  in  certain 
cases  will  he  considered  further  on. 

That  the  condition  of  nutrition  in  many  cases  is  not  influenced,  and  in 
other  Buffers  more  or  Less  severely,  has  been  already  mentioned.  This  varia- 
tion in  the  condition  of  the  general  health  bears  no  direct  relation  to  the 
amount  of  the  urinary  secretion. 

A-  thirst  is  uniformly  present  so  also  the  appetite  is  often  enormous. 
Ehrhardl  relates  the  case  of  a  patient  who  consumed  L2  beefsteaks  for  break- 
fast and  II  portions  of  meat  at  his  midday  meal.  It  i-  self-evident  that  in 
these  individuals  the  composition  of  the  urine  will  deviate  from  the  ordinary 
in  that  the  amount  of  the  dissolved  constituents  will  he  decidedly  greater 
than  the  normal.  French  authors  describe  diabete  n:<>tiiri</ur  as  an  inde- 
pendent affection  differing  from  the  ordinary  diabetes  by  an  increase  of 
NT-excretion.  It  i-  very  probable  that  a  lame  number  of  cases  included  in  this 
group  represent  really  rack  cases  of  diabetes  insipidus  a-  were  blessed  with  an 
appetite  of  the  variety  just  mentioned.  At  any  rate,  in  recent  time-,  when 
pathology  has  not  only  considered  excretion  hut  also  metabolism  a-  a  whole, 
no  cases  of  diabetes  insipidus  bave  been  reported  in  which  albumin  decompo- 
sition was  decidedly  greater  than  the  albumin  intake. 

Frequently  with  an  improvement  in  the  general  condition,  the  abnor- 
mally great  appetite  also  disappears. 

9 


114  DIABETES  INSIPIDUS 

In  contrast  to  these  cases,  there  are  others  in  which  the  amount  of  nour- 
ishment consumed  is  very  slight,  and  in  which  nevertheless  the  body-weight 
is  maintained.  Quite  a  number  of  observations  have  been  recorded  which 
show  that  adults  can  maintain  their  N-equilibrium  upon  a  diet  containing 
remarkably  small  quantities  of  albumin  (35  grams  in  a  person  weighing  55 
kilograms). 

In  most  cases,  however,  the  quantity  of  nutriment  is  about  the  normal 
amount. 

Quite  frequently  in  patients  suffering  from  diabetes  insipidus,  the  tem- 
perature is  found  to  be  conspicuously  low.  Whether  this  is  simply  to  be  re- 
garded as  the  result  of  a  profuse  ingestion  of  cool  drink  cannot  be  decided. 
In  view  of  the  diminished  metabolism  which  may  be  observed  in  some  of  the 
patients,  we  must  consider  the  possibility  that  the  diminution  in  the  body 
warmth  is  to  be  referred  to  a  lessened  oxidation,  such  as  occurs  in  old 
people. 

In  contrast  with  this,  an  enormously  increased  body-weight  has  been  re- 
ported in  isolated  eases. 

Disturbances  on  the  part  of  the  organs  of  circulation,  such  as  cardiac 
hypertrophy,  apparently  do  not  occur;  on  the  other  hand,  the  digestive  appa- 
ratus is  sometimes  damaged  by  the  profuse  ingestion  of  fluids.  Gastric 
catarrh,  especially,  develops  not  infrequently;  true  gastrectasis  is  only  noted 
exceptionally. 

'The  psychic  functions  do  not  appear  to  suffer  serious  disturbance,  although 
hypochondriacal  and  melancholic  attacks  are  frequently  met  with.  In  the 
cases  which  run  their  course  with  decided  implication  of  the  somatic  condi- 
tion, these  psychic  disturbances  are  the  rule.  Occasionally,  in  diabetes  in- 
sipidus occurring  in  youth,  a  general  retardation  of  mental  development  is 
observed. 

Of  other  nervous  disturbances,  only  sciatica  is  to  be  mentioned  as  a  com- 
paratively frequent  complication  of  diabetes  insipidus. 

In  the  main,  the  diabetic  does  not  appear  more  predisposed  to  general  or 
organic  disease  than  are  healthy  individuals.  The  reports  that  he  is  particu- 
larly susceptible  to  all  sorts  of  infectious  diseases,  and  that  he  is  very  liable 
to  be  attacked  by  tuberculosis,  have  not  been  confirmed  by  the  study  of  more 
complete  statistics. 

Only  with  one  disease  is  there  a  close  connection  which  must  be  somewhat 
more  minutely  considered;  I  mean  diabetes  mellitus.  This  may  be  in  vari- 
ous ways. 

The  connection  is  clearest  in  the  cases  of  diabetes  due  to  disease  of  the 
brain.  A  number  of  cases  are  on  record  in  which,  after  trauma  to  the  head, 
true  diabetes  mellitus  with  an  increased  urinary  flow  first  appeared,  the  sugar, 
however,  disappearing  after  a  few  weeks,  and  then  for  a  long  period,  some- 
times for  years,  a  simple  polyuria  persisted.  We  know  from  Claude  Bernard's 
experiments  that  the  region,  injury  to  which  gives  rise  to  polyuria,  is  situated 
only  a  few  millimeters  above  the  glycogenic  area ;  later  investigations  by  Eck- 
hard have  shown  that  in  rabbits  by  lesions  in  the  region  of  the  sinus  rhom- 
boidalis,  sometimes  glycosuria,  sometimes  polyuria,  may  be  produced.     It  is 


SYMPTOMS  AND  CLINICAL  COURSE  115 

therefore  quite  plain  that  this  cerebral  form  of  diabetes  insipidus  is  intimately 
related  to  diabetes  mellitus. 

But  even  in  the  non-cerebral  cases  of  diabetes  insipidus  we  can  often  recog- 
nize a  relationship  to  saccharin  diabetes,  especially  when  we  note  the  transi- 
tion from  the  one  disease  to  the  other,  and  the  occurrence  of  both  diseases  in 
members  of  the  same  family.  Typical  examples  of  such  occurrence  have  been 
collected,  particularly  by  Senator,  and  to  these  he  has  added  cases  observed  by 
himself.  It  is  quite  probable  that  in  these  instances  the  neuropathic  constitu- 
tion represents  the  connecting  link. 

The  results  of  animal  experiments  also  suggest  the  possibility  of  a  rela- 
tion between  diabetes  insipidus  and  diabetes  mellitus.  During  increased  (ex- 
periment) diuresis,  no  matter  whether  it  is  due  to  drugs  or  to  a  simple  injec- 
tion of  water,  sugar  is  often  found  in  the  urine.  Probably  the  sugar  is  simply 
swept  along  with  the  current.  In  man  no  well-attested  examples  of  this  purely 
secondary  appearance  of  sugar  in  permanent  polyuria  have  been  observed,  and 
the  attempts  to  produce  alimentary  glycosuria  in  diabetes  insipidus  by  an 
increased  ingestion  of  sugar  do  not  favor  the  view  thai  such  a  washing  out  of 
sugar  occurs  readily  in  this  disease. 

As  we  go  on  from  this  sketch  of  the  disease  to  the  special  varieties  of  the 
malady  and  their  course,  simple  polyuria  in  cerebral  diseases  must  be  first 
considered. 

This  combination  is  not  frequent;  about  80  cases  may  be  collected  from 
literature.  They  are  connected  mos!  often  with  injuries  to  the  bead:  secondly 
with  brain  tumor-,  then  with  softening,  while  the  reel  are  divided  among 
various  other  cerebral  affections,  hemorrhage,  encephalitis,  meningitis,  etc. 

In  the  overwhelming  majority  of  cases,  the  lesion  is  found  to  be  in  the 
posterior  part-  of  the  brain,  mostly  in  the  region  of  the  pons  or  the  fourth 

Ventricle,    i.e..    e-perially    ill.    or    at     le,'l-t     ill    the    vicinity    of.    tile    at'ea     ill    which 

Claude  Bernard  and  Eckhard  were  able,  by  experimental  lesions,  to  produce 
in  animals  transitory,  and  Kahler  permanent,  polyuria.  Kahler  collected 
from  literature  25  cases  after  trauma  to  the  head,  and  2  1  following  other  cere- 
bral diseases,  and  added  one  of  cadi  variety  from  his  own  observations;  among 
the  22  cases  of  the  second  group,  I  occurred  in  disease  of  the  pons,  2  from 
compression  of  the  pons,  2  from  compression  of  the  sinus  rhomboidalis  by 
tumor.  :;  in  diffuse  disease  of  the  medulla  oblongata;  1  was  probably  due  to 
a  lesion  of  the  medulla  oblongata,  1  to  a  cerebellar  tumor.  2  to  syphilis  of  the 
brain,  and  1  to  disease  of  the  corpora  quadrigemina. 

Less  frequently,  in  cases  of  trauma  to  the  head,  the  region  of  the  Binus 
rhomboidalis  is  found  to  be  the  seat  of  the  lesion;  the  description  in  the  few 
necropsies  is  not  clear.  On  the  other  hand,  in  all  of  these  eighl  cases  there 
occurred  other  cerebral  symptoms  (particularly  paralysis  of  the  abducens) 
which  point  with  great  likelihood  to  a  lesion  in  the  pons. 

Hence,  although  diabetes  insipidus  is  found  especially   in  those  cerebral 

diseases   which    affeel    the   medulla    oblongata,   the   pon8,   or   the    middle  brain. 

nevertheless,  upon  accurate  investigation  of  the  individual  observations,  we 
lind  no  Bingle  area  in  the  brain  which  ha-  l n  uniformly  affected,  and,  on 


116  DIABETES  INSIPIDUS 

the  other  hand,  a  great  number  of  observations  show  that  every  one  of  the 
previously  mentioned  areas  may  be  affected  without  polyuria  appearing. 

We  must,  therefore,  admit  that  although  we  can  find  cases  which  are  in 
accord  with  Claude  Bernard's  celebrated  experiments,  and  although  the  cases 
of  diabetes  mellitus  occurring  in  connection  with  cerebral  disease  have  turned 
out  to  be  associated  with  a  lesion  of  the  very  area  in  the  floor  of  the  fourth 
ventricle  which  was  discovered  in  Bernard's  experiments,  nevertheless  we 
cannot  speak  of  diabetes  insipidus  in  the  same  sense  that  we  do  of  aphasia 
as  a  focal  symptom,  meaning  that  it  occurs  invariably  in  lesions  of  this 
area. 

In  the  majority  of  cases,  diabetes  insipidus  first  appears  at  a  relatively 
advanced  stage  of  the  cerebral  disease,  i.  e.,  after  other  cerebral  symptoms  have 
developed.  In  some  cases,  on  the  other  hand,  polyuria  has  been  the  only 
symptom  for  months.  This  has  been  observed  several  times  in  tubercular 
meningitis,  in  tumors  of  the  brain,  and  in  cerebral  softening. 

A  similar  polyuria  has  been  noted  after  trauma  to  the  head,  usually  asso- 
ciated with  other  cerebral  symptoms.  Almost  always  the  injuries  are  severe 
and  are  followed  by  complete  loss  of  consciousness  for  several  days.  The  in- 
crease of  urine  usually  appeared  for  the  first  time  after  consciousness  had 
returned ;  comparatively  often  the  signs  that  the  seat  of  the  cranial  lesion  was 
in  the  posterior  brain  were  paralyses  of  the  muscles  of  the  eye.  Such  a  polyuria 
arising  after  injuries  to  the  head  sometimes  disappears  with  the  other  cere- 
bral symptoms,  while  in  other  cases  it  persists  as  the  only  morbid  phenomenon 
for  a  varying  period  of  time,  even  for  many  years. 

The  form  of  diabetes  insipidus  which  occurs  in  connection  with  cerebral 
affections  usually  leads  only  to  a  moderate  increase  in  the  amount  of  the  urine. 
In  the  traumatic  cases  the  daily  excretion  of  urine  amounts  to  from  5  to  20 
liters;  in  the  form  occurring  in  non-traumatic  cranial  disease,  from  5  to  10 
liters  are  excreted.  There  are  no  peculiarities  in  the  behavior  of  the  polyuria 
which  distinguish  these  cerebral  cases  from  other  types  of  polyuria.  Variations 
in  the  intensity  of  the  urinary  disturbances  occur,  but  are  for  the  most  part 
slight ;  it  is  but  little  influenced  by  drugs  or  other  therapeutic  measures.  The 
general  health  appears  but  slightly  affected  by  the  polyuria  itself,  apart  from 
the  influence  of  the  cerebral  disease. 

There  is  only  one  peculiarity  of  the  cerebral  form,  and  this  is  its  relation 
to  diabetes  mellitus,  which,  as  we  have  already  mentioned,  is  apparently  more 
distinctive  than  in  other  forms  of  the  affection. 

Among  the  functional  neuroses  in  which  diabetes  insipidus  is  frequently 
observed,  two  are  of  importance :  epilepsy  and  hysteria. 

In  epilepsy,  polyuria  usually  develops  gradually,  after  the  underlying  dis- 
ease has  existed  for  years;  more  rarely  it  appears  suddenly  in  connection 
with  the  attack.  Usually  it  reaches  but  a  moderate  grade,  and  as  a  rule  it 
is  more  susceptible  to  treatment  than  the  cerebral  form. 

The  mariner  in  which  epilepsy  develops  and  its  different  stages  are  without 
any  discernible  influence  on  the  polyuria.  That  diabetes  insipidus  occurs  in 
connection  with  a  particular  form  of  epilepsy  (e.  g.,  one  suspected  to  depend 


SYMPTOMS  AND  CLINICAL  COURSE  117 

on  an  organic  cerebral  affection)  has  not  been  determined  by  any  reliable 
evidence  up  to  date. 

The  cases  associated  with  epilepsy  are  not  very  frequent.  In  contrast  to 
this,  those  combined  with  hysteria  form  a  very  large  group.  It  is  true  that 
there  are  great  differences  of  opinion  in  regard  to  our  right  to  associate  many 
of  these  cases  with  hysteria.  The  earlier  writings  on  this  subject  were  based 
on  a  careful  collection  of  cases  from  literature,  and  a  few  cases  were  described 
in  detail  as  a  proof  of  the  possibility  of  a  combination  of  hysteria  and  diabetes 
insipidus;  lately,  with  a  number  of  authors,  there  is  rather  a  tendency  to  class 
the  bulk  of  such  cases  under  hysteria,  and  we  even  read  that  practically  all 
cases  not  due  to  organic  cerebral  lesions  are  of  a  hysterical  nature.  The  latter 
view  seems  too  extreme;  but  it  is  really  difficult  to  draw  the  line  correctly. 
We  know  that  "normal"  diabetes  insipidus  leads  invariably  to  various  psy- 
chical anomalies,  slight  in  themselves  (nervous  irritation,  hypochondriacal 
conditions  and  melancholia).  Hence  it  may  be  difficult  subsequently  to  deter- 
mine how  far  symptoms  of  this  kind  should  be  referred  to  diabetes  insipidus, 
and  how  far  they  should  be  ascribed  to  an  hysteria  which  has  existed  for 
some  time. 

Diabetes  insipidus  develops  in  the  course  of  hysteria  either  gradually  or 
quite  suddenly  after  nervous  irritation,  fright,  or  worry,  or  sometimes  directly 
after  a  severe  hysterical  attack.  In  the  latter  cases  it  must  be  remembered  that 
the  hysterical  attack  is  always  followed  by  the  profuse  discharge  of  clear 
urine,  typical  urina  spastica,  that,  therefore,  a  certain  tendency  to  polyuria 
accompanies  any  such  attack  and  is  included  in  the  conception  of  hysteria. 

Some  cases  of  diabetes  insipidus  occur  in  profoundly  hysterical  individuals 
whose  disease  has  existed  for  years,  and  who  exhibit  severe  spasms,  paralyses, 
and  similar  symptoms.  Examples  of  this  form  have  been  particularly  de- 
Bcribed  by  French  authors;  curiously  it  is  more  often  seen  in  men  than  in 
Wimen. 

More  frequently,  at  least  in  Germany,  polyuria  appears  in  persons  in  whose 
previous  history  slight  signs  of  hysteria  are  found,  or  in  those  in  whom  exami- 
nation reveals  hysterical  stigmata,  such  as  anesthesia,  hyperalgesia  of  the  skin, 
mucous  membranes,  or  ovaries,  limitation  of  the  fields  of  vision,  and  increased 
reflexes. 

That  we  are  not  dealing  in  such  cases  with  a  mere  coincidence  of  two  dis- 
eases entirely  independent  of  one  another,  and  that  the  diabetes  insipidus  may 
be  a  real  symptom  of  the  hysteria,  has  been  demonstrated  several  times  very 
clearly  by  the  intluenceof  hypnosis.  l'>y  this  means  polyuria  has  been  made  to 
disappear  suddenly,  and  later  to  reappear  as  before.  Matthieu  mention-  a 
very  Bignificanl  case  which  was  cured  by  the  administration  of  powders  con- 
taining nothing  but  sodium  ehlorid,  hut  which  later  relapsed  when  the  patient 
discovered  the  deception. 

In  most  of  the  hysterical  cases,  we  are  dealing  apparently  with  pure  poly- 
dipsia, as  has  already  been  mentioned,  and  in  fad  the  majority  of  cases  of 
polydipsia  appear  to  belong  to  this  group,  viz.:  to  hysterical  diabetes.  Bui  the 
reverse  of  this  statemenl  is  not  correci  ;  cases  of  pure  primary  polyuria  may 
also  be  caused  by  hysteria. 


118  DIABETES  INSIPIDUS 

Hysterical  polyuria  occurs  most  frequently  in  adults  between  the  third  and 
fourth  decades  of  life.  It  is  rare  in  adolescents  and  children,  but,  neverthe- 
less, Terrier  reports  two  undoubted  instances  in  children  aged  one  and  a  half 
and  two  and  a  half  years  respectively. 

In  this  hysterical  polyuria,  as  in  the  other  forms,  the  patient  is  much  more 
inconvenienced  by  constant  thirst  and  the  frequent  desire  to  urinate  than  by 
actual  pathologic  symptoms ;  but  there  are  exceptions  to  this  rule.  Some  per- 
sons in  whom  the  further  course  of  the  disease  justifies  the  diagnosis  "  hys- 
terical polyuria  "  emaciate  decidedly  as  long  as  the  diabetes  exists.  This  is, 
however,  unusual.  As  a  rule,  nutrition  and  the  general  well-being  are  not 
disturbed.  Variations  in  the  degree  of  polyuria  are  frequent ;  often  the  course 
of  the  polyuria  is  parallel  with  the  severity  of  the  other  hysterical  phenomena. 

Hysterical  polyuria  may  be  cured,  and  sometimes  with  surprising  rapid- 
ity. Occasionally  this  occurs  spontaneously,  more  frequently  after  the  employ- 
ment of  various  drugs  (valerian,  antipyrin,  etc.),  by  suggestion,  under  true 
hypnosis,  or  by  means  of  powders  of  sodium  chlorid  and  similar  placebos. 
Indeed,  it  is  often  this  rapid  cessation  of  the  malady  after  such  slight  external 
causes  that  stamps  the  condition  with  certainty  as  hysteria. 

But  by  no  means  all  cases  of  hysterical  diabetes  terminate  so  promptly. 
Many  cases  are  protracted  over  long  periods  of  time.  In  quite  a  number  the 
history  states  only  that  at  the  time  of  the  patient's  discharge  the  diabetes  con- 
tinued unimproved.  In  such  cases  the  disease  appears  to  last  for  decades. 
In  another  series  it  disappears  gradually  in  the  course  of  a  few  weeks  under 
appropriate  antihysteric  treatment,  or  more  rarely  it  ceases  spontaneously. 

Diabetes  insipidus  in  hysterical  subjects  shows  very  varying  behavior.  In 
some,  the  symptoms  point  decidedly  to  a  primary  increase  of  renal  activity. 
This  is  especially  shown  by  the  dryness  of  the  skin  and  the  slight  tendency  to 
sweating.  In  other  patients,  on  the  contrary,  perspiration  is  profuse,  occa- 
sionally so  free  that  they  complain  of  it.  If  we  are  still  in  doubt,  in  such 
instances,  whether  the  decided  excretion  of  water  through  the  skin  can  be 
explained  by  a  primary  renal  insufficiency  or  whether  the  increased  excretion 
of  water  is  a  phenomenon  coordinate  with  the  increased  activity  of  the  kid- 
neys, the  study  of  a  further  group  of  cases  distinctly  proves  that  this  lrysterical 
polyuria  is  really  the  consequence  of  an  increased  ingestion  of  water,  i.  e.,  a 
condition  of  primary  polydipsia.  A  number  of  such  cases  are  susceptible  of 
cure  by  a  more  or  less  compulsory  limitation  of  the  intake  of  water,  without  the 
patients  undergoing  any  great  hardship.  Sometimes  we  have  only  to  quiet 
the  thirst  with  simple  remedies,  such  as  stewed  prunes  or  small  quantities  of 
lemonade,  in  order  to  control  the  polyuria.  Such  cases  appear  to  represent 
scarcely  more  than  a  bad  habit,  and  the  number  of  these  cases  may  in  reality 
be  much  greater  than  can  be  determined  from  the  clinical  histories  in  litera- 
ture because  proof  (i.  e.,  the  therapeutic  test)  cannot  be  obtained. 

As  the  third  main  group  the  idiopathic  form  of  diabetes  insipidus  will 
next  be  considered,  i.  e.,  that  form  in  which  no  other  organic  or  functional  dis- 
turbance can  be  found  as  a  cause  for  the  polyuria.  According  to  its  mode  of 
origin  we  may  subdivide  this  group  into : 


SYMPTOMS   AND  CLINICAL  COURSE  119 

(a)  A  hereditary  group, 

(b)  A  group  occurring  in  connection  with  acute  diseases, 

(c)  The  group  of  cases  which  appear  after  psychical  irritation, 

(d)  A  group  of  cases  in  which  the  causes  are  various  or  quite  un- 
known. 

The  hereditary  form  has  been  observed  only  in  isolated  instances,  but  a 
few  times  in  an  extraordinarily  striking  way.  The  most  remarkable  series  of 
observations  we  owe  to  Weil.  He  found  23  diabetics  among  91  members  of 
a  family  which  embraced  -1  generations,  namely,  the  ancestor,  3  children,  7 
grandchildren,  and  12  great-grandchildren;  the  heredity  was  always  a  direct 
one,  never  skipping  a  generation;  men  and  women  wore  affected  to  a  similar 
extent.  Undue  thirst  was  noted  in  some  of  these  individuals  even  as  nurs- 
lings; besides  the  breast-milk,  it  was  necessary  to  administer  water;  in  others 
the  condition  first  arose  between  the  second  and  fourth  years  of  life.  Almost 
all  members  of  the  family  possessed  a  good  constitution  and  enjoyed  good 
health;  many  readied  extreme  old  age. 

There  are  also  other  records  of  the  occurrence  of  diabetes  insipidus  in  three 
or  four  successive  generations,  the  individuals  remaining  mentally  and  phys- 
ically healthy,  apart  from  the  anomaly  in  question. 

With  comparative  frequency,  i.e.,  in  about  10  per  cent,  of  all  cases,  dia- 
betes  insipidus  appears  after  acute  infectious  diseases  (scarlatina,  measles, 
diphtheria,  malaria,  rheumatic  fever,  etc.)  ;  most  of  these  cases  (like  those 
just  discussed)  appeared  to  cause  but  slight  disturbance  of  health.  They  are 
of  theoretic  interest  from  the  fact  that  convalescence  in  these  same  infectious 
diseases  is  quite  commonly  associated  with  an  increase  in  the  excretion  of 
urine.  It  appears  therefore  that  permanent  polyuria  may  arise  from  a  nor- 
mal transitory  polyuria,  just  as  it  does  in  hysterical  individuals  who  have 
paroxysms  with  urina  spastica.  Similarly,  permanent  polyuria  may  appear 
alter  the  temporary  employment  of  diuretic  remedies  which  cause  a  powerful 
diuresis. 

In  a  number  of  cases  diabetes  insipidus  has  occurred  as  a  sequel  of  vari- 
ous deleterious  factor-;  extreme  cold  or  heat  and  sunstroke  are  mentioned  as 
causes.  More  frequently  alcoholic  excesses,  bodily  injuries  (excluding  head 
injuries),  and  psychical  trauma  are  mentioned. 

We  include  this  entire  group  with  the  idiopathic  form  of  diabetes.  But  in 
many  cases  doubl  may  arise  whether  they  might  nol  be  grouped  as  well,  or 
better,  with  hysteria.  Ever  if  Qone  of  the  definite  stigmata  of  hysteria  is 
found,  and  if  the  course  of  the  affection  does  not  decidedly  favor  this  diag- 
nosis, we  often  meet  with  striking  proofs  that  the  patients  belong  to  the 
category  of  neuropathic  individuals.  They  react  in  this  peculiar  way  to  rela- 
tively feeble  irritations  which  in  the  normal  individual  would  be  without  effect, 
and.  when  once  produced,  the  abnormal  activity  of  the  kidneys  continue-  for 
a  long  time.  We  often  succeed  in  discovering  from  the  history  thai  certain 
abnormalities  have  preceded  these  pathological  reaction-.  Griffouilleree  points 
to  the  fact  thai  in  youth  enuresis  nocturna  has  often  preceded  the  condition. 
Numerous  therapeutic  experiment-  Lead   us  to  rasped   that   the  aeuropathic 

element    play-   a    prominent    rule   in    the  etiology  of   these    formfl   of   diabetes. 


120  DIABETES  INSIPIDUS 

Hence,  even  if  we  do  not  consider  this  type  of  diabetes  as  belonging  to  hys- 
teria, we  must  look  upon  it  as  closely  related. 

In  this  category  we  also  include  the  cases  in  which  diabetes  insipidus  occurs 
in  pregnancy.  A  typical  example  of  this  kind  is  reported  by  Janzen  from 
v.  Mering's  clinic,  in  which  a  woman  in  three  successive  pregnancies  was 
attacked  by  a  severe  form  of  diabetes  insipidus  (passing  15  liters  of  urine, 
whereas  she  ordinarily  voided  but  2  to  3  liters). 

The  belief  that  such  cases  are  closely  related  to  the  hysterical  group  is 
not  simply  a  matter  of  theoretic  classification  but  has  an  important  influence 
on  the  choice  of  treatment  to  be  employed  and  the  energy  with  which  it  is  to 
be  carried  out. 

A  number  of  cases  remain  in  which  none  of  the  previously  mentioned  fac- 
tors comes  into  question,  and  in  which  the  malady  progresses  slowly,  frequently 
becomes  very  severe,  and  comparatively  often  leads  to  decided  loss  of  strength 
and  to  emaciation.  These  forms  have  mostly  been  looked  upon  as  typical  cases 
of  diabetes  insipidus.  In  the  majority  of  these,  observations  regarding  metab- 
olism and  the  influence  of  varying  quantities  of  fluid  ingested  have  been  made. 
For  the  most  part  such  cases  are  serious;  as  a  rule,  attempts  at  cure  are 
unavailing  or  have  only  a  transitory  effect.  Nevertheless,  life  is  preserved 
and  the  nutrition,  which  at  first  suffers  severely,  improves  again  without,  how- 
ever, reaching  the  normal. 

Occasionally,  decided  permanent  impairment  of  health  has  been  observed, 
but  marasmus  increasing  in  severity  until  the  disease  terminates  in  death  is 
rare.  Earlier  literature  contains  more  frequent  reports  of  an  unfavorable  out- 
come. Indeed,  Trousseau  believed  diabetes  insipidus  to  be  almost  invariably 
fatal.  During  the  last  decades,  however,  it  seems  that  no  instances  of  the 
kind  have  been  published ;  perhaps  a  case  reported  by  Strubell  belongs  to  this 
group. 

As  a  rule,  in  these  severe  cases  of  diabetes  insipidus  the  constitutional  con- 
dition appears  to  go  hand  in  hand  with  the  psychical.  Permanent  psychical 
depression,  hypochondriacal  and  melancholic  conditions,  are  frequent  and 
almost  constantly  accompanying  phenomena.  We  may  even  be  impelled  to 
ask  whether  a  psychical  anomaly  is  not  the  fundamental  condition,  and  the 
diabetes  insipidus  only  a  symptom. 

Nevertheless,  such  severe  cases  are  rare;  the  majority  of  idiopathic  cases 
lead  a  fairly  comfortable  life  for  years. 

The  cases  of  diabetes  insipidus  developing  from  syphilis  appear  to  occupy 
a  position  quite  apart.  A  number  of  instances  of  this  kind  are  known  in 
which,  besides  the  diabetes,  there  were  various  symptoms  pointing  to  organic 
disease  of  the  brain,  and  in  some  of  these  the  necropsy  showed  the  presence  of 
gummata  or  of  meningitis.  In  addition  to  these,  there  are  cases  in  which 
diabetes  insipidus  develops  during  the  course  of  syphilis,  sometimes  many  years 
after  infection  has  taken  place  and  without  any  other  cerebral  symptoms. 
By  antisyphilitic  treatment  this  form  of  the  affection  has  several  times  been 
made  to  disappear  promptly.    It  is  therefore  scarcely  questionable  that  it  was 


DIAGNOSIS  121 

due  to  syphilis.  Whether  we  are  to  assume  in  these  cases  a  gumma  of  the 
brain  (the  simultaneous  existence  of  destructive  gummata  of  the  skin  in  one 
of  these  patients  appears  to  favor  this  view),  or  whether  we  are  to  assume 
a  disturbance  in  the  function  of  the  kidney  due  to  syphilis,  is  very  difficult  to 
determine  at  present.  The  practically  important  point  is  this,  that  in  the 
course  of  syphilis,  with  or  without  cerebral  symptoms,  simple  polyuria  may 
occur,  and  that  antiluetic  treatment  in  both  instances  may  bring  about  a  cure 
of  the  diabetes  insipidus. 

DIAGNOSIS 

The  diagnosis  of  diabetes  insipidus  is  usually  easy;  the  important  symp- 
tom, polyuria,  can  be  readily  determined,  care  being  taken  not  to  confound 
the  disease  with  other  conditions  in  which  polyuria  also  occurs.  Diabetes 
mellitus  may  easily  be  excluded  by  an  examination  for  sugar.  The  question 
whether  or  not  contracted  kidney  is  present  is  not  always  so  promptly  solved. 
<';im'~  <»f  chronic  nephritis  in  which  the  urine  is  at  times  free  from  albumin 
are  not  very  rare;  but  the  examination  of  the  heart,  and  particularly  the 
hardness  of  the  pulse,  will  generally  lead  to  a  correct  diagnosis.  It  is  note- 
worthy that  in  diabetes  insipidus,  in  spite  of  the  fact  that  plethora  serosa 
occurs  frequently,  hi/pcrtrophy  of  the  heart  and  changes  in  the  tension  of  the 
pulse  never  result. 

Difficulties  in  the  exclusion  of  nephritis  may,  however,  arise  in  an  oppo- 
site direction,  namely,  from  the  presence  of  slight  quantities  of  albumin  in  the 
urine  in  diabetes  insipidus.  A  number  of  clinical  histories  which  describe 
otherwise  typical  cases  of  diabetes  insipidus,  some  of  the  hysterical  type,  con- 
tain the  statement  that  periodially  small  quantities  of  albumin  could  be 
detected  in  the  urine.  It  is  difficult  to  exclude  nephritis  in  these  eases  as  they 
have  not  coin.'  to  autopsy;  aevertheless  the  fact  remains,  that  cases  which  in 
their  course  and  especially  in  their  uniform  benignity  do  not  differ  from  the 
ordinary  picture  of  simple  polyuria  may  from  time  to  time  show  traces  of 
albumin  in  the  urine. 

Amyloid  kidney,  less  often  than  contracted  kidney,  may  lead  to  confu- 
Bion;  although  occasionally  albuminuria  is  absent  here,  the  general  condition, 
the  enlargement  of  the  liver  and  spleen,  make  the  diagnosis  clear. 

Arteriosclerosis  more  often  Leads  to  diagnostic  difficulties,  as  it  tends 
decidedly  to  increase  the  amount  of  the  urine;  but  here  also  the  action  of  the 
heart  and  pulse  i-  conclusive. 

chronic  pyelitis  musl  also  be  considered  in  the  differential  diagnosis;  in 
Bome  feu-  cases  of  diabetes  insipidus  described  in  literature,  one  cannot  help 
Buspecting  that  the  writers  were  really  portraying  cases  of  pyelitis.  The 
reports  that  the  urine  always  contained  slight  traces  of  albumin  and  a  puru- 
lent sediment  are  significant. 

Finally,  the  possibility  that  diabetes  insipidus  may  he  mistaken  for  the 
results  of  a  simple  increase  of  the  intake  of  fluid  must  he  considered. 

As  a  matter  of  fact  this  differentiation,  at  lea-t  for  a  time,  may  he  simply 
impossible;   the  limits  vary  and  are  partially  arbitrary.     If  after  simply  dimin- 


122  DIABETES  INSIPIDUS 

ishing  the  amount  of  fluid  ingested,  the  polyuria  ceases,  and  never  recurs, 
as  is  sometimes  the  case  in  the  hysterical  form  of  diabetes  insipidus,  it  depends 
ultimately  upon  the  option  of  the  observer  whether  the  case  is  classed  as  one 
of  bad  habit,  or  as  diabetes  insipidus;  for  diabetes  is  so  comprehensive  an 
entity  that  such  cases  as  the  above  can  be  included  under  it.  In  fact,  literature 
contains  quite  a  numbe^  of  such  examples. 

TREATMENT 

Treatment  may  be  carried  out  in  various  ways.  Where  possible,  we  should 
search  for  the  underlying  condition  which  results  in  polyuria,  and  an  attempt 
should  be  made  to  remove  this. 

In  diabetes  due  to  cere  oral  causes,  such  treatment  is  practicable  only  in 
isolated  instances.  Nevertheless,  a  case  is  on  record  in  which,  during  the 
course  of  an  apparently  mild  pulmonary  tuberculosis,  acute  polyuria  appeared, 
later  followed  by  pain  and  stiffness  in  the  cervical  vertebras,  then  paralysis  of 
both  arms  and  legs;  here  the  diabetes  was  cured,  simultaneously  with  the 
paralysis,  by  treatment  with  Glisson's  suspension. 

Otherwise,  among  the  cerebral  cases  of  diabetes  insipidus,  apart  from  the 
traumatic  which  not  infrequently  get  well  without  treatment,  only  those 
depending  upon  cerebral  syphilis  are  to  be  considered;  in  these  cases  and  all 
others  complicated  by  syphilis  (whether  a  definite  cerebral  lesion  exists  or 
not),  a  cure  may  be  effected  by  the  use  of  iodin  and  mercury,  as  has  been 
previously  mentioned. 

Somewhat  more  uncertain  are  the  cases  occurring  in  the  course  of  hys- 
teria. The  fact  that  hypnotism  sometimes  brings  about  a  prompt  cure  is  a 
proof  of  the  purely  functional  nature  of  these  cases,  and  of  the  possibility  of 
an  "  etiologic  therapy "  by  purely  psychical  treatment.  Whether  or  not  in 
every  hysterical  case,  or  in  every  case  that  is  suspected  of  being  hysterical, 
hypnotism  is  to  be  employed,  is  a  question  that  must  be  answered  according 
to  the  confidence  of  the  physician  in  the  harmlessness  of  this  remedial  agent. 
In  point  of  fact,  in  Germany  no  reports  of  cures  of  this  kind  have  been  made. 

On  the  other  hand  a  number  of  measures  of  a  more  innocent  nature 
directed  against  the  general  nervous  condition  have  often  been  quite  success- 
ful. Among  these  are,  first,  general  dietetic  measures,  sufficient  exercise  in 
the  open  air,  and  proper  employment;  occasionally,  change  of  climate  has 
been  successful ;  often  diabetes  has  been  seen  to  disappear  or  become  less 
marked  in  the  course  of  hydrotherapeutic  treatment.  Eegulated  cold  ablu- 
tions, douches,  baths,  in  the  milder  cases  can  be  carried  out  at  the  patient's 
own  home,  in  the  severe  cases  in  hydropathic  institutes ;  lukewarm  baths  appear 
to  have  a  similar  effect. 

Among  drugs  which  seem  to  be  of  use  in  a  similar  way,  antipyrin  (3  grams 
daily)  and  valerian  are  the  favorites;  the  latter,  given  up  to  20  grams  of 
the  powdered  root,  is  sometimes  decidedly  beneficial;  also  potassium  bromid, 
assafetida,  and  camphor,  employed  from  the  same  point  of  view,  have  occa- 
sionally been  very  useful. 

The  remedies  just  mentioned  are,  a  priori,  most  useful  in  the  cases  in 


TREATMENT  123 

which  diabetes  insipidus  occurs  in  hysterical  individuals.  Regarding  the 
prompt  action  of  valerian,  as  veil  as  of  quite  a  number  of  remedies  to  be 
mentioned  later  on,  the  success  of  which  is  reported  in  the  journals  every  year, 
it  is  unquestioned  that  diabetes  insipidus  is  very  often  only  a  symptom  of  hys- 
teria which,  like  other  hysterical  symptoms,  may  disappear  after  the  use  of 
the  most  varied  remedies;  as,  for  instance,  after  the  employment  of  powders 
of  simple  sodium  chlorid,  provided  only  that  simultaneously  the  necessary 
psychic  influence  is  exerted.  Many  cases,  perhaps  most  of  those  that  come 
under  treatment  at  all,  occur  in  individuals  whose  malady  cannot  positively 
be  included  in  the  category  of  hysteria,  yet  is  closely  related  to  this  group 
of  affections,  and  these  people  are  known  as  "  nervous  persons  "  in  the  ordi- 
nary sense  of  the  term.  In  them,  as  well  as  in  frankly  hysterical  cases,  success 
comparatively  often  follows  the  use  of  the  previously  mentioned  remedies. 

Other  drugs  have  been  employed  with  the  hope  of  influencing  the  circula- 
tion in  the  kidneys;  the  amount  of  urine  in  the  main  depends  upon  the  height 
of  the  blood-pressure  in  the  glomeruli,  and  the  more  contracted  the  small  renal 
arteries  are  the  less  is  the  amount  of  blood  which  readies  the  glomeruli.  A.S 
the  principal  representative  of  such  artery-constricting  remedies,  ergotin  has 
frequently  been  administered  in  diabetes  insipidus,  particularly  in  the  last 
few  years,  as  its  action  has  been  much  praised.  Lead  acetate  and  tannin 
are  less  useful. 

A  tropin  and  other  belladonna  preparations,  which  are  supposed  to  act  more 
directly  upon  the  secretion  of  the  kidneys,  have  also  an  inhibiting  secretory 
influence  upon  most  of  the  other  glands.  This  influence,  unfortunately,  is 
more  obvious  in  the  salivary  gland-  than  in  the  kidneys;  at  Least,  increased 
dryness  of  the  mouth  and  correspondingly  great  thirsl  have  been  observed 
more  often  than  decrease  in  the  amount  of  the  urine. 

Electricity  has  been  employed  for  the  sake  of  its  (supposedly)  direcl  influ- 
ence upon  the  renal  function.  As  irritation  of  the  cervical  curd  diminishes 
renal  secretion  in  animal  experiments  (on  account  of  it-  powerful  contraction 
of  the  va.-a  afferentia)  the  attempt  has  been  made  to  diminish  the  amount  of 
urine  in  man  by  galvanization  of  the  cervical  cord.  More  recently  we  have 
attempted  to  make  the  current  act  directly  upon  the  kidneys  (both  electrodes 
in  the  renal  region).  Whether  the  electrical  current  thus  applied  has  any 
real  action  is  very  difficult  to  decide;  it  i-,  however,  a  fact  that  tin-  treatment 
i-  often  quite  successful. 

Another  method  by  which  we  have  tried  to  diminish  renal  secretion  is  by 
stimulating  the  excretion  of  water  by  ihr  shin.  It  has  been  frequently  noted 
thai  the  steam  bath  is  conspicuously  grateful  to  the  diabetic,  although  it 
diminishes  the  secretion  of  urine:  other  patients  report  that  they  feel  much 
better  during  the  hot  season  than  during  the  cold.  Among  the  remedies  which 
stimulate  secretion  by  the  skin,  sweat  baths  and  pilocarpin  are  to  be  consid- 
ered; the  former  certainly  have  transitorily  an  ameliorating  effect.  Permanent 
ami  complete  cure  has  not  been  observed;  but  decrease  in  subjective  discom- 
fort and  diminution  in  the  daily  amount  of  urine  have  been  noted.  The  -ante 
is  true  of  pilocarpin.  polyuria  decidedly  decreasing  with  it<  employment  (in- 
jections of  from  0.01  to  0.015  on  two  successive  days).     It  is  true  that  in  other 


124  DIABETES  INSIPIDUS 

cases  the  remedy  has  been  ineffectual,  and  of  course  it  will  always  be  futile  in 
persons  who  readily  perspire. 

Finally,  that  method  of  treatment  must  be  considered  which  perhaps 
appears  to  be  the  most  obvious,  the  limitation  of  the  intake  of  fluid.  This 
has  often  been  tried  by  the  patients  themselves,  but,  as  regards  the  propriety 
and  success  of  such  attempts  at  cure,  the  views  of  different  authors  are  dia- 
metrically opposed. 

In  some  cases  withdrawal  of  water,  strictly  adhered  to,  acts  with  great 
rapidity;  the  patients  are  better  almost  from  the  first  day,  and  after  a  few 
days  may  be  looked  upon  as  permanently  cured.  These  are  the  cases  which  we 
have  designated,  upon  the  basis  of  this  sort  of  improvement,  as  primary  poly- 
dipsia. Very  characteristic  is  a  case  described  by  Westphal :  primarily  for  the 
purpose  of  studying  her  condition,  the  intake  of  fluid  was  limited,  and  at  the 
conclusion  of  the  experiment  the  disease  was  cured.  In  other  cases  the  same 
result  has  been  attained  by  a  gradual  diminution  of  drink. 

However,  it  is  only  with  a  small  number  of  diabetics  that  we  so  readily 
reach  the  goal.  Most  patients  cannot  endure  the  tormenting  thirst,  and  with 
or  without  the  knowledge  of  the  physician  they  will  drink  water.  In  such 
patients,  this  method  of  treatment  can  be  carried  out,  and  with  it  sometimes 
an  actual  cure  attained,  by  isolation  and  observation.  Geigel  reports  such  a 
case  of  diabetes  insipidus  in  which  during  the  first  few  days  of  treatment 
severe  disturbances  appeared,  but  the  withdrawal  of  water  was  persisted  in, 
and  after  a  short  time  the  case  could  be  looked  upon  as  almost  cured. 

For  the  cases  of  diabetes  insipidus,  sensu  strictiori,  in  which  the  polyuria 
actually  depends  upon  increased  renal  secretion,  such  attempts  at  cure  by  the 
withdrawal  of  water  are  rarely  successful.  Indeed  there  is  reason  to  fear  that 
we  do  harm  by  a  dangerous  inspissation  of  the  blood.  Unfortunately  it  is 
often  difficult  in  practice  to  decide  between  the  two  forms,  and  this  is  true 
of  the  majority  of  cases,  i.  e.,  of  those  that  are  symptomatic  of  hysteria  or  at 
least  have  some  connection  with  it.  Despite  this  difficulty,  and  in  order  to 
achieve  success  wherever  possible,  it  is  advisable  to  attempt  with  all  patients 
of  this  type  a  methodical  and  cautious  withdrawal  of  water.  Of  course  this 
can  hardly  be  carried  out  except  in  thoroughly  organized  hospitals. 


GOUT 
By  W.   EBSTEIN,  Göttingen 

The  words  "  Gicht  "  and  "  Zipperlein  "  are  genuine  German  words.  The 
former  is  the  equivalent  of  the  old  English  masculine  "  ghida,"  which  means 

"bodily  pain  in  general."    Zipperlein  is  the  diminutive  of  "Zipper,"  fori 1 

from  the  verb  "  zippern,"  which  in  German  means  "  jerking,  restless,  trip- 
pin;/."  The  term  "  Zipperlein  "  has  been  used  in  German  for  "  Gicht  "  since 
the  fifteenth  century.  It  was  invented  by  sufferers  from  this  disease  in  a  sort 
of  grim  humor.  It  is  quite  certain  that  the  word  "  Gield  "  is  not,  as  was  sup- 
posed,  in  etymological  relation  with  the  English  word  "gout,"  or  with  words 
of  the  same  derivation  in  the  Romanic  languages  (the  French  "  goutte,"  the 
Italian  "gotta,"  the  Spanish  "  gota").  These  designations  cannot  be  re- 
jected, as  they  have  become  established  by  usage,  but  that  they  are  not  to  be 
looked  upon  as  appropriate  every  one  must  admit.  They  are  based  upon  tin- 
old  pathological  conception  that  gout  was  caused  by  a  peculiar  humor  distilled 
from  the  blood,  which,  drop  by  drop,  was  exuded  into  the  joints,  a  view  for 
the  support  of  which  no  proof  of  any  kind  can  be  adduced.  The  designation 
"Zipperlein"  for  gout  has  quite  properly  been  excluded  from  scientific 
nomenclature,  as,  in  a  Symptomatologie  connection,  a  uniform  meaning  is  not 
attached  to  it.  Among  the  ancients,  the  pathologic  term  "gout"  was  em- 
braced  in  the  collective  term  "arthritis"  under  which  every  form  of  arthritic 
inflammation  was  included.  The  term  "arthritis"  for  "gout"  embraces  bo 
much  more  than  the  purely  Symptomatologie  conception  that  it  include-;  a 
very  important  and  active  constituent  of  gout,  namely,  the  "inflammation" 
of  a  joint.  The  words  podagra,  ehiragra,  gonagra,  omagra,  ischiagra  and 
rachisagra,  were  applied  by  the  ancients  to  joint  pains  in  differed  regions  of 
the  body,  and  pains  chiefly  due  to  gouty  and  rheumatic  affection-  were  thus 
designated. 

Certainly  to-day,  when  we  speak  of  podagra,  we  mean  only  a  gouty  affec- 
tion of  the  foot.  The  word  "arthritis"  of  the  ancients  alone  discloses  noth- 
ing a-  tu  the  etiology  of  the  joint  inflammation.  Later  an  attempt  was  made 
t<>  separate  the  various  arthritic  inflammations  according  t<>  their  cause,  and 
after  we  had  demonstrated  the  causal  relation  of  uric  acid  and  it-  combina- 
tion  with  alkalies   to   Lroiif,  the  term   arthritis   urica,  <»r   nralira   was  given    to 

gouty  joint  inflammations.  As,  however,  there  are  ~till  differences  of  opin- 
ion on  this  point,  it  would  perhaps  l"'  wiseT  to  speak  only  of  gouty  joint 
inflammations,  or,  for  one  who  is  fond  of  foreign  designations,  of  gouty 

arthritis. 

188 


126  GOUT 

The  name  gout  has  the  advantage  that  it  indicates  nothing  more  than  the 
pain  which  always  plays  a  prominent  role  in  gouty  affections. 

It  must  be  remembered,  however,  that  in  gout  we  are  not  dealing  with  pain 
that  is  restricted  to  the  joints,  but  with  a  general  pain  which  is  well  described 
by  Trousseau,  "  totum  corpus  est  podagra."  We  shall  refer  to  this  more 
minutely  when  we  consider  the  clinical  aspect  of  gout. 

Gout  is  certainly  a  disease  of  antiquity.  It  is  not  my  intention  here  to 
discuss  in  detail  the  historical  aspect  of  the  disease.  A.  Delpech  has  recently 
written  quite  a  voluminous  work  (678  pages)  on  the  history  of  gout  and  of 
rheumatism,  in  which  he  dwells  upon  the  antiquity  of  the  disease,  and  brings 
it  down  to  the  time  of  Thomas  Sydenham  (1624—1089).  In  the  study  of  the 
clinical  history  of  gout,  we,  as  a  rule,  only  go  back  to  the  time  of  Sydenham, 
and,  it  appears  to  me,  quite  properly  so.  Sydenham's  description  is  an  account 
of  his  own  illness,  for,  when  he  wrote  his  dissertation,  he  had  already  been 
suffering  from  gout  for  thirty-four  years.  All  that  had  been  written  prior  to 
Sydenham's  time  regarding  the  symptomatology  of  gout  was  of  little  value 
compared  with  what  Sydenham  communicated  to  us.  The  elucidation  of  the 
cause  and  the  cure  of  gout  Sydenham  bequeathed  to  posterity. 

THE   PATHOGENESIS   OF    GOUT 

The  pathogenesis  of  gout  has  been  studied  from  many  points,  and  is  now 
by  preference  our  subject  of  investigation.  It  was  the  theme  which  occupied 
the  attention  of  the  Section  on  Internal  Medicine  of  the  Xlllth  Medical  Con- 
gress in  Paris.  I  was  unable  to  perform  the  task  allotted  to  me,  and  give  a 
synopsis  of  this  subject  at  the  Congress;  but,  at  Easter-tide,  1900,  I  sent  to 
the  Secretary  of  the  Section  of  Internal  Medicine  a  compilation  setting  forth 
my  views,  and  it  may  not  now  be  out  of  place  briefly  to  discuss  the  present 
standing  of  the  question  as  set  forth  in  this  thesis.  The  views  expressed  by 
me  were  as  follows : 

1.  Gout  is  a  more  or  less  chronic  disease  which  develops  upon  the  basis 
of  a  pathologic  predisposition  which  is  hereditary  and  generally  congenital, 
and  is  usually  designated  the  uric  acid  diathesis. 

2.  Regarding  the  ultimate  cause  of  the  uric  acid  diathesis,  merely 
hypotheses  can  be  at  this  time  proposed.  The  intimate  relations  existing 
between  the  nucleins  and  uric  acid  make  it  appear  likely  that  in  the  uric  acid 
diathesis  there  is  an  abnormal  composition  of  the  cell  nucleus;  that  is,  of  the 
protoplasm  in  the  person  in  question.  It  is  quite  evident  that  an  individual 
predisposition  which  may  assert  itself  through  entire  families  and  races  is  a 
prominent  factor  in  the  uric  acid  diathesis. 

3.  Various  circumstances  appear  to  show  that  true  gout  develops  from 
the  uric  acid  diathesis.  Regarding  these  circumstances  the  following  may  be 
mentioned : 

(a)  The  more  pronounced  the  uric  acid  diathesis  in  a  person,  the  earlier, 
that  is,  the  more  decidedly,  ceteris  paribus,  will  gout  develop  in  him. 

(b)  There  are  habits  which  favor  the  appearance  of  gout;  among  these 
are  indolence  and  high  living,  especially  the  combination  of  these,  and,  of 


THE  PATHOGENESIS  OF  GOUT  127 

prime  importance,  the  use  of  alcohol.  In  the  main,  the  periodic  variations 
which  have  been  reported  as  to  the  frequency  of  gout  may  lie  referred  to  this. 

(c)  There  are  acute  and  chronic  intoxications  as  well  as  infections,  which, 
in  combination  with  the  uric  acid  diathesis,  favor  the  development  of  gout, 
and  in  which  bacterial  toxins  also  may  play  a  part.  I  shall  first  mention  the 
relations  of  gout  to  rheumatism,  to  syphilis,  and  to  lead  intoxication.  Influ- 
enza, also,  appears  to  predispose  to  gout. 

(d)  Contagion,  as  was  first  asserted  by  no  less  an  authority  than  Boer- 
haave,  does  not  seem  to  play  any  part  in  gont. 

(e)  Climatic  conditions  apparently  have  no  influence  upon  the  develop- 
ment of  gout. 

4.  The  poison  which  causes  gout,  the  actual  materia  peccans,  appears  to 
be  uric  acid.  Whether,  besides  this,  other  products  of  metabolism  of  the  group 
of  alloxur  and  nuclein  bases  are  operative,  or,  as  some  authors  assume,  a 
poison  the  nature  of  which  is  unknown,  is  still  an  open  question.  It  is  likely 
that  only  the  endogenous  nuclein  substances  of  the  human  body,  and  not  the 
uric  acid  originating  from  the  nucleins  of  the  food,  have  a  direct  influence 
upon  the  pathogenesis  of  gout.  Whether  an  increased  formation  of  uric  acid 
occurs  in  gout  has  not  been  proven  with  certainty,  nor  do  I  believe  this  proof 
to  be  absolutely  necessary.  Nevertheless,  I  consider  such  increase  to  be  prob- 
able. That  an  increased  production  of  uric  acid  (which  we  assume  from  an 
increased  excretion)  does  not  alone  give  rise  to  gout  is  taught  by  the  study 
of  leukemia.  In  some  cases  of  this  disease,  as  is  well  known,  more  uric  acid 
is  excreted  than  in  any  cases  of  gout. 

5.  Uric  acid  is  a  chemical,  but  not  a  septic,  poison.  Its  action  is  not  uni- 
form in  all  species  of  animals,  at  different  ages  in  the  same  animal,  nor  in 
their  different  organs.    Uric  acid  produces  inflammation  and  necrotic  chai 

in  the  affected  tissues,  and  finally  causes  complete  death  of  the  tissue  (necro- 
sis). Only  after  the  tissue  is  wholly  necrotic  does  a  deposit  of  crystalline 
uric  acid  take  place  in  the  form  of  acid  -odium  urate  (monosodium  urate. 
Tollens,  sodium  biurate,  Robert.-).  According  to  Tollens.  uric  acid  also  circu- 
lates in  the  blood  and  in  the  alkaline  juices  of  the  tissue  in  the  same  alkaline 
combination,  and  not.  as  Roberts  has  assumed,  as  sodium-quadriurate,  a  com- 
bination which  Tollens  more  technically  designates  as  hemisodium-urate.  It 
i-  ad  mit  teil  at  once  that  monosodium-urate,  Tollen-  ( sodium-biurate,  Robert- ). 
under  otherwise  similar  condition-  may  also  be  deposited  as  crystals  in  tissues, 
where  not  uric  acid  itself  bui  another  poison  has  caused  necrosis. 

6.  To  understand  the  pathogenesis  of  the  differenl  Bymptoms  of  gout,  we 
mu-t  distinguish  between  (a)  primary  arthritic  goul  and  (&)  primary  renal 
gout.  The  first  i-  by  far  the  more  frequent,  and  the  Bufferers  from  this  often 
reach  extreme  old  age.  Primary  arthritic  gout  tir-t  develops  under  the  influ- 
ence of  a  localized  uric  acid  -ta-i-.  i.e.,  it  is  limited  to  one  or  more  pari-  of 
the  human  body.  In  primary  renal  gout  we  have  from  the  onsel  a  general 
uric  acid  -ta-i-.  which,  therefore,  affects  all  parts  of  the  body,  and  is  invariably 
due  to  a  primary  and  severe  disease  of  the  kidney. 

Tt  is  evident  fn-m  the  Transactions  of  the  Section  of  Internal  Medicine 
of  the  XI  Nth  Intei-national  Medical  Congress,  that  tl pinions  of  the  two 


128  GOUT 

reviews  differed  decidedly  from  my  own,  just  mentioned,  as  I  think  I  suffi- 
ciently emphasized  in  my  theses;  yet,  as  the  subject  is  a  very  difficult  one, 
this  diversity  of  views  is  not  to  be  wondered  at.  Nevertheless,  our  views  have 
so  much  in  common  that  we  may  hope,  sooner  or  later,  to  come  to  some  agree- 
ment regarding  the  most  important  points  in  the  pathogenesis  of  gout.  I  base 
my  remarks  upon  the  review  in  the  "  Semaine  medicale,"  No.  30,  1900,  pp. 
202,  203,  which  reports  the  address  of  the  reviewer,  Dr.  Le  Gendre,  and  of  the 
co-reviewer,  Sir  Dyce  Duckworth. 

Of  course,  if  Sir  Dyce  Duckworth  believes  that  the  kidney  is  the  only 
organ  in  which  the  synthesis  of  uric  acid  is  carried  out,  i.  e.,  in  which  uric  acid 
is  formed — in  which  opinion  he  and  his  countryman  Luff  occupy  quite  an 
isolated  position  not  only  among  pathologists  but  also  among  physiologists 
— unanimity  in  regard  to  the  most  important  question  in  the  pathogenesis  of 
gout  is  not  to  be  arrived  at.  Sir  Dyce  Duckworth  maintains,  with  Garrod, 
that  uric  acid  is  the  materia  peccans  in  gout  and  that  the  latter  results  from 
a  hindrance  to  the  excretion  of  uric  acid  through  a  faulty  action  of  the  kid- 
ney which  can  by  no  means  be  demonstrated  from  anatomically  determinable 
changes.  Sir  Dyce  Duckworth,  therefore,  in  all  cases  of  gout,  assumes  a 
uricemia  from  a  faulty  excretion  of  uric  acid.  Le  Gendre  laid  great  stress 
in  his  paper  upon  the  influence  of  functional  disturbances  of  the  kidney  in 
the  production  of  gout  and  also  referred  to  the  functional  disturbances  of  the 
nervous  system;  these  result  in  nutritive  changes  in  the  tissue  and  cells, 
and  thereby  cause  irregularity  in  the  formation,  that  is,  in  the  excretion,  of 
toxic  products  of  metabolism  from  the  influence  of  which  gout  develops.  In 
regard  to  these  doubtful  points  in  the  pathogenesis,  it  appears  to  me  advisable 
to  wait  for  the  publication  of  Le  Gendre's  complete  paper.  On  the  other  hand, 
there  are  a  number  of  factors  which  may  be  designated  as  occasional  causes  of 
gout,  particularly  family  predisposition  and  the  influence  of  the  mode  of  life, 
etc.,  concerning  which  there  is  complete  unanimity. 

Instead  of  voluminous  descriptions,  it  will  best  serve  our  purpose  to  cite  a 
few  cases  from  practice. 

Observation  I. — Dr.  X.,  from  H.,  a  physician  about  thirty-nine  years  of  age,  con- 
sulted me  June  22,  1900,  on  account  of  gout.  About  fifteen  years  before,  while  he  was 
a  medical  student,  I  had  repeatedly  treated  him  for  this.  As  a  jolly  fraternity  student, 
he  probably  drank  more  beer  than  was  good  for  him,  and  had  acquired  a  decided  embon- 
point at  too  early  an  age.  In  addition  to  a  plentiful  use  of  alcohol,  he  ate  a  great  deal, 
and  took  very  little  exercise.  In  spite  of  these  facts  he  was  by  no  means  dissipated,  but 
passed  a  very  good  examination,  and  is  now  an  extremely  busy  practitioner.  The 
patient's  family  has  a  predisposition  to  gout ;  although  his  parents  did  not  suffer  from 
it,  his  maternal  grandfather  late  in  life  had  a  severe  form  of  gout,  and  two  of  his 
maternal  uncles  also  suffered  from  it. 

As  early  as  between  his  sixteenth  and  eighteenth  years,  the  patient  had  repeated 
attacks  of  cramps  in  the  calves,  and  he  is  inclined  to  regard  as  "  gouty  "  an  attack  of 
"  stiff  knee  "  which  appeared  in  his  boyhood  after  a  salt-water  bath,  and  was  accompanied 
by  very  severe  pain.  The  first  typical  attack  occurred  in  his  twenty-first  year,  in  the 
metatarsal  phalangeal  joint  of  the  right  great  toe.  The  attacks  recurred  twice  in  the 
next  year;  the  fourth  attack,  in  June,  1885,  which  was  accompanied  with  fever,  was 
more  severe  than  the  preceding  ones.  The  fifth  attack,  in  September,  1885,  which 
appeared  three  days  after  "  turning  "  the  left  foot,  was  localized  in  the  first  metatarsal 


THE  PATHOGENESIS   OF   GOUT  129 

phalangeal  joint.  This  ran  its  course  within  three  days,  was  mild,  and  accompanied 
with  only  slight  redness  and  swelling  of  the  affected  joint  and  no  disturbance  of  his 
general  health.  After  the  patient  began  the  practice  of  medicine  he  had  no  attack  of 
gout  for  years.  He  lost  his  excessive  weight,  and  when  1  met  him  in  consultation  a 
number  of  years  ago  I  was  astonished  to  find  him  rather  thin.  Be  followed  minutely 
my  dietetic  regulations,  and  under  this  treatment  only  "premonitions"  of  his  old 
trouble  occurred.  His  constantly  increasing,  very  extensive  and  exhausting  practice 
now  made  it  impossible  for  him  to  live  in  accordance  with  the  rules  previously  followed. 
The  attacks  of  gout  recurred,  and  in  the  winter  of  1899-1900  he  suffered  almosl  every 
two  months  from  severe  typical  attacks,  with  violent  onset,  and  constantly  accompanied 
with  fever.  But  while  these  formerly  lasted  for  a  few  weeks,  they  now  disappeared  in 
a  few  days.  These  paroxysms  were  always  associated  with  large  effusions  into  the 
joints,  and  the  seat  of  the  attacks  was  in  the  toe  and  the  talocrural  joint  upon  both  Bides. 
The  attacks  were  cured  by  the  use  of  wine  of  Colchicum  seed,  potassium  iodid  and  sodium 
bicarbonate.  Pain  in  the  right  shoulder  joint,  however,  which  had  troubled  him  off  and 
on  for  some  time,  now  became  chronic.  The  influence  of  trauma  in  the  occurrence  of 
typical  gout  was  shown  when,  upon  April  30,  1900,  the  patient  fell  from  hi-  bicycle, 
causing  a  contusion  of  the  right  talocrural  and  of  the  left  knee  joint.  As  early  as  the 
next  day,  in  both  of  the  previously  mentioned  joints,  a  typical  attack  of  gout  developed 
which  affected  t he  patient  greatly.  He  never  had  venereal  disease;  he  smokes  much — 
according  to  report-  8  mild  cigars  daily — and  consumes  a  bottle  of  light  wine  daily, 
but  no  beer.  The  patient  considers  the  wine  necessary,  as.  without  it.  he  has  inter- 
mittent heart  action.  Appetite  and  digestion  are  good.  His  maximum  weight  was  in 
1883,  when  he  weighed  20!)  pounds;  now  he  weighs  17G  pounds.  During  the  alt 
the  urine  is  said  to  be  scant  and  dark  in  color,  but  returns  to  the  normal  after  the 
paroxysm  has  passed  ofT.  Albumin  and  sugar  have  never  been  present.  The  patient, 
when  I  examined  him,  had  a  pulse  of  G4.  cardiac  dulness  was  not  increased,  the  second 
aortic  sound  was  loud  but  not  quite  clear.  Organic  changes  were  not  evident.  The 
patient  was  very  much  enfeebled,  and  as  he  desired  to  undergo  a  bath  and  mineral 
spring  treatment,  I  advised  him  to  go  first  to  the  Allgan  Alps  at  Obersdorf.  On  the 
I'd  of  August,  1900,  the  patient  wrote  me  from  the  " Nebelhornhaus "  (2,251  meters 
high),  stating  that  he  felt  very  well  there  and  that  without  much  trouble  he  could 
climb  quite  high  mountains.  Besides  the  observance  of  a  strict  dietetic  regime,  absti- 
nence from  alcohol  and  a  decided  limitation  of  smoking  were  required. 

Tin-  case  jusl  cited  is  in  many  respects  interesting,  und  I  shall  take  oppor- 
tunity to  n-vcrt  to  it  later.  At  this  time,  only  the  factors  which  bear  upon 
the  pathogenesis  of  gout  are  to  be  considered.  We  note  that  the  family  predis- 
positioD  of  'lie  patient  was  only  in  the  ancestral  line  of  the  mother,  the  latter 
herself  remaining  Tree  from  the  affection.  The  maternal  grandfather  and  two 
of  the  maternal  uncles,  on  the  other  hand,  had  gout.  A-  the  clinical  history 
Bhows,  the  patient  was  inclined  to  «late  the  beginning  of  his  disease  from  his 
youth.  It  is  evident  that  g<>ut  may  come  on  early  in  life.  A  very  skilful 
physician  who  had  suffered  from  gout,  hut  who  died  of  a  severe  diabetes  mel- 
litus complicated    by    nephritis,    told    me   that    even    in    hi,    ninth    vear  he   had 

Beizures  of  so-called  rheumatism  in  the  hall  <>f  the  great  tor  of  hi-  left  foot. 
In  children,  attack-  of  gout  frequently  follow  trauma,  and  it  has  Keen  main- 
tained that  gout  i-  the  consequence  of  trauma.  A-  a  matter  ..!'  fact.  I  have 
seen  gout  in  adolescents,  hut  always  in  boys,  an  observation  which  i<  confirmed 
by  medical  literature.  The  cramps  in  tin-  calves  with  which  my  patient  was 
affected  between  his  sixteenth  and  eighteenth  years  mav.  in  consideration  <<( 
the  course  which  the  disease  took,  !»■  regarded  a-  premonitory  gouty  Bymptoms. 
Prom  tin-,  however,  and  also  from  numerous  other  experiences  at  hand,  it 

10 


130  GOUT 

cannot  be  doubted  that  the  abuse  of  alcohol  during  his  student  days,  as  well 
as  the  previously  mentioned  obesity,  conduced  to  the  development  of  the  gouty 
paroxysms.  But  it  must  be  emphasized  that,  in  my  patient,  the  later  disap- 
pearance of  his  corpulence  did  not  lead  to  the  cessation  of  the  gout.  Obesity 
is,  therefore,  not  a  prerequisite  for  the  production  of  gout,  although  they 
may  occasionally  occur  in  combination,  sometimes  with  diabetes  mellitus  as 
well.  Of  further  interest  in  my  patient's  history  is  the  fact,  that  in  proportion 
as  he  deviated  from  the  mode  of  life  advised  by  me,  the  latent  gout,  i.  e.,  the 
gouty  diathesis,  asserted  itself  by  the  appearance  of  repeated  paroxysms,  and 
that  the  last  attack  of  this  kind  occurred  after  a  fall  from  a  bicycle  whereby 
he  sustained  a  contusion  of  the  left  knee-joint  and  of  the  right  talocrural. 
I  do  not  consider  this  occurrence  of  a  gouty  paroxysm  after  trauma  as  b}r  any 
means  accidental.  Opposed  to  its  being  a  mere  coincidence  is  the  frequency  with 
which  this  combination  appears.  My  patient  is  a  physician  in  easy  circum- 
stances. We  know  that  the  wealthy  minority,  the  so-called  "  upper  ten  thou- 
sand," are  most  frequently  the  subjects  of  gout.  Among  our  hospital  patients 
who,  for  the  most  part,  belong  to  the  poorer  classes  of  the  population,  gout 
has  heretofore  been  looked  upon  as  a  rare  affection.  I  saw  a  poor  tailor  in  the 
Hospital  of  the  Home  for  Incurables  in  Breslau,  who  showed  extensive,  partly 
ruptured  gouty  tophi.  Yet  when  I  review  the  cases  of  gout  accumulated  dur- 
ing my  long  professional  service  in  the  Hospital,  the  number  of  the  poor  is 
quite  small  when  compared  with  those  in  better  circumstances  whom  I  have 
seen  in  consultation  and  in  my  private  hospital.  In  this  connection,  there 
has  lately  been  a  remarkable  change  in  Germany,  and  one  which  is  food  for 
thought.  Albert  Fraenkel,  in  the  Beport  of  the  Medical  Division  of  the 
Hospital  Urban  in  Berlin,  from  the  year  1896  to  1897,  and  among  1,706  male 
patients,  has  observed  24  cases  of  arthritis  uratica.  In  the  hospitals  of  Eng- 
land, previous  to  this,  the  number  of  gouty  patients  was  a  striking  one.  In 
the  years  1874  to  1876,  in  the  Medical  Division  of  St.  George's  Hospital  in 
London,  among  4,695  patients,  not  less  than  97  cases  of  gout  were  present, 
while,  in  the  same  period  of  time,  in  the  Munich  Medical  Clinic,  among  4,670 
patients,  there  were  only  11  cases  of  gout.  We  might  say,  it  is  true,  that  in 
this  coincidence  plays  a  leading  role.  But  it  must  be  observed  that  in  the 
same  period  of  time,  and  in  nearly  the  same  number  of  patients,  in  a  London 
Hospital,  there  were  almost  nine  times  as  many  cases  of  gout  as  in  the  Munich 
Hospital.  If  it  is  true  that  in  Munich,  upon  the  average,  more  than  200  liters 
of  beer  per  capita  of  the  population  are  yearly  consumed,  the  conclusion  must 
be  drawn  that  the  influence  attributed  to  Munich  beer  in  the  development  of 
uric  acid  gout  must  be  regarded  as  erroneous  during  the  period  just  men- 
tioned. The  reports  of  His,  Jr.,  and  Magnus-Levy  favor  the  increase  of  gout 
among  the  poorer  population  of  Germany.  Among  the  poor  people  of  Leipsic 
the  former  not  infrequently  saw  gout.  The  latter,  in  the  Out-Patient  Medical 
Clinic  in  Strassburg,  made  the  same  observation.  Nevertheless,  the  social  posi- 
tion, that  is,  the  wealth  or  poverty  of  the  individual — hence  his  mode  of  life — 
has  no  fundamental  influence  upon  the  development  of  gout.  The  special 
disposition  of  the  person  which  is  noted  in  other  members  of  the  same  family, 
even  in  entire  races,  and  which  may  be  hereditary,  is  the  important  point.     It 


THE   PATHOGENESIS  OF   GOUT  131 

is  evident  that  the  presence  of  so-called  predisposing,  favoring  factors  is  nol 
alone  sufficient  for  the  development  of  gout. 

In  this  connection,  Thomas  Oliver  alludes  in  his  valuable  hook.  "  Lead 
Poisoning/'  to  an  investigation  regarding  the  workmen  in  the  Large  Lead  works 
at  Newcastle-on-Tyne,  and  this  is  very  characteristic.  As  is  well  known,  lead 
is  a  predisposing  factor  in  the  development  of  gout.  Yet  such  of  the  workers 
in  lead  at  Xewcastle-on-Tyne  as  come  from  the  north  of  England  arc  only 
rarely  attacked  by  gout,  even  when  their  kidneys  are  diseased,  for  in  that  por- 
tion of  the  population  the  predisposition  to  gout  is  absent;  while  those  who 
come  from  the  south  of  England,  where  the  gouty  predisposition  is  widely 
distributed,  are  frequently  attacked  with  gout  when  employed  in  the  pre- 
viously mentioned  lead  works  in  the  north  of  England.  One  problem  referred 
to  by  me  in  the  above  named  theses  on  the  pathogenesis  of  gout  requires 
further  discussion:  in  what  does  the  predisposition  to  gout  consist,  and  how 
is  the  so-called  gouty  predisposition,  the  uric  acid  diathesis,  to  he  conceived? 
The  principal  role  is  played  by  a  faulty  composition,  not  of  the  "humors/5 
the  juices  of  the  human  body,  but  of  the  protoplasm  including  the  nuclei  of 
the  cells,  in  consequence  of  which  uric  acid,  and  perhaps  still  other  bodies 
of  the  group  of  the  alloxur  and  nuclein  bases,  are  either  formed  in  increased 
amounts  or  in  an  unusual  region.  I  believe  it  to  be  very  likely  that  the  simul- 
taneous occurrence  of  both  these  anomalies  is  the  rule.  The  organs  richest  in 
nuclein  play  the  mo-t  important  part  in  this  process,  and  1  believe  we  may 
assume  from  the  clinical  history  of  gout  that  hone  marrow  and  the  greal  mus- 
cular masses  of  the  human  body,  especially  those  of  the  extremities,  are  in- 
volved in  this  anomaly  of  uric  acid  formation.  It  is  quite  possible  that  in 
these  tissues,  already  rich  in  nuclein  substance,  an  increased  formation  of 
alloxur  or  nuclein  bases,  that  is,  of  uric  acid,  takes  place.  Mv  investigations 
have  shown  thai  uric  acid  is  a  chemical  poison,  and  hence,  until  the  same  has 
been  proven  of  the  other  previously  named  substances,  and  until  the  question 
has  been  answered  whether  there  is  a  specific  "goul  poison/'  as  is  believed 
by  some  authors,  uric  acid  may  be  looked  upon  as  the  materia  peccans  in  gout. 
The  uric  acid.  Loosely  combined  with  an  alkali  formed  in  the  muscles  and  hone 
marrow,  is  dissolved,  (lows  through  the  lymph  and  blood  channels,  and  is  for 
the  mosl  part  excreted  by  the  kidneys,  unless  oilier  processes  of  decomposition 
take  place  during  its  course.  If  this  process  of  excretion  occurs  smoothly  and 
without  hindrance,  and  if  the  gouty  predisposition  LS  m>i  too  decided,  the  con- 
Bequences  of  the  existing  anomaly  of  metabolism  will  Bhow  themselves  only 
after  a  certain  time  by  a  number  of  pathological  phenomena,  mild  <»r  severe, 
Bubjective  and  objective.  Bui  as  soon  as  any  intercurrenl  cause  produces 
stasis  of  the  juices  rich  in  uric  acid  in  the  affected  area — naturally  at  lir-t  in 
the  peripheral  parts,  particularly  in  the  lower  extremities,  in  which  stasis  is 
especially  prone  to  happen — engorgement  will  occur  which,  in  consequence  of 
this  Local  stasis,  also  primo  loco,  in  the  affected  pari-  of  the  body,  will  become 
more  or  Less  noticeable  as  a  typical  attach  of  gout.  I  call  these  cases  primary 
arthritic  gout.  In  Observation  I.  we  have  a  case  of  primary  arthritic  goul 
which  should  more  correctly  be  designated  primary  extremity  gout,  since  not 
only  the  joints  were  implicated,  but  also  the  muscles,  and  especially  the  -kin. 


132  GOUT 

Besides  the  extremities,  in  this  form  of  gout  the  most  distant  parts  of  the 
body,  i.  e.,  those  situated  at  the  actual  periphery,  are  implicated,  as,  for  in- 
stance, the  concha  auris.  For  the  explanation  of  these  phenomena  in  primary 
extremity  (arthritic)  gout,  an  insufficiency  of  the  kidneys  which  causes  gen- 
eral uric  acid  stasis  is  by  no  means  necessary.  Following  Garrod's  reasoning, 
this  is  still  frequently  assumed,  although  the  reasons  mentioned  by  him  have 
been  shown  to  be  incorrect.  We  shall  revert  to  this  later.  Besides  this  pri- 
mary extremity  (arthritic)  gout  there  is  also  a  primary  renal  gout.  Here, 
in  consequence  of  a  primary  severe  renal  affection,  most  likely  based  upon  a 
gouty  predisposition,  there  is  an  incapacity  on  the  part  of  the  kidneys  to  ex- 
crete the  waste  of  metabolism,  i.  e.,  the  uric  acid.  Consequently  a  generalized 
uric  acid  stasis  develops  which  affects  all  the  parts  of  the  body.  The  patients 
frequently  die  before  a  typical  attack  of  gout  occurs.  They  succumb,  there- 
fore, to  the  renal  affection,  usually  while  still  young,  whereas  in  primary 
extremity  (arthritic)  gout  they  will  live  to  old  age.  In  primary  arthritic  gout 
the  kidneys  suffer  as  well  as  all  the  other  organs ;  but  there  are  numerous  cases 
of  primary  arthritic  gout  in  which  the  patients  die  from  intercurrent  diseases, 
and  in  which  the  kidneys  show  absolutely  nothing  abnormal.  Primary  arthritic 
gout  is  fortunately  by  far  the  most  frequent  form  of  the  disease,  and  the 
one  we  shall  first  consider.  Formerly  it  was  thought  absolutely  necessary  to 
differentiate  various  forms  of  gout,  I  do  not  think  it  expedient  to  dilate  upon 
this  point,  and  will  only  mention  that  to-day  designations  are  not  infrequently 
used  for  some  of  these  varieties,  between  which  no  important  differences  exist : 
thus  we  hear  of  latent  gout,  larval  gout,  pseudo-localized  gout,  retrocedent 
gout,  etc.  Yet  I  have  not  been  satisfied  with  Garrod's  differentiation  of  a 
regular  and  an  irregular  form;  even  in  professional  practice  it  does  not  sim- 
plify the  condition. 

SYMPTOMATOLOGY 

We  will  now  discuss  the  symptomatology  of  primary  arthritic  gout,  and  in 
order  to  make  the  condition  clear  I  shall  include  the  necessary  pathologico- 
anatomical  data.  I  shall  retain  the  designation  primary  arthritic  gout,  as  in 
the  great  majority  of  cases  the  joint  symptoms  are  still  the  most  prominent, 
and  as  I  do  not  desire,  by  another  designation,  further  to  complicate  a  subject 
which  is  already  rich  in  superfluous  names.  To  avoid  prolixity,  in  enumerating 
the  possible  limitations  in  the  pathogenesis  of  gout,  among  the  noxa  which 
produce  it  I  shall  refer  exclusively  to  uric  acid  as  the  materia  peccans.  This 
materia  peccans  which  produces  the  disturbances,  the  totality  of  which,  there- 
fore, forms  the  gouty  symptom-complex,  is  in  part  a  purely  functional  dis- 
turbance, for  which  up  to  the  present  no  constant  pathologico-anatomical 
material  lesion  is  known ;  in  part,  however,  a  disturbance  for  which  the  mate- 
rial substratum  has  been  discovered.  The  latter  depends  in  some  degree 
upon  inflammatory,  also  upon  degenerative,  changes  in  the  organs  and  tissues. 
Suppurative  processes  are  not  produced  by  uric  acid;  it  is  not  a  septic,  but 
chiefly  a  chemical,  poison.  The  degenerative  changes  in  gout  from  the  influ- 
ence of  uric  acid  show  nothing  characteristic  of  gout  until  necrosis  of  the 


SYMPTOMATOLOGY  133 

affected  tissue  occurs.  If  tissue  necrosis  has  taken  place,  then  acid  sodium 
urate  is  deposited  in  the  form  of  crystalline  needles.  That  necrosis  of  the 
tissue  is  the  primary  condition  is  shown  from  the  fact  that  the  necrosed  area 
is  larger  than  the  urate  deposits.  Around  the  necrotic  areas,  more  or  less 
round  cell  infiltration  is  often  found.  I  have  proven  that  such  gout  foci,  i.  e., 
necroses  with  crystalline  urates  (completely  analogous  processes),  may  be 
experimentally  produced  in  hirds.  In  these  experiments  urate  deposits  also 
occur  to  a  greater  or  less  extent  in  normal  tissue,  i.e.,  in  tissue  which  has 
not  become  necrotic.  Of  course,  this  has  absolutely  no  connection  with  gout, 
but  merely  explains  the  post  mortem  finding  that,  with  cessation  of  life,  the 
tissues  are  saturated  with  urates,  and  these  are  excreted  in  a  crystalline  form. 

The  symptoms  of  primary  gout  are  as  follows:  In  primary  arthritic  goul 
the  first  phenomena  are  the  manifestations  of  the  gouty  predisposition.  They 
may  he  designated  as  the  premonitory  or  initial  symptoms  and  they  precede 
the  first  attack.  It  is  possible  that  where  the  predisposition  is  not  very  great, 
and  especially  where  an  exciting  cause  is  lacking,  these  so-called  premonitory 
-ymptoms  of  gout  may  remain  the  only  ones,  so  that  a  true  gouty  paroxysm 
does  not  develop  at  all.  Generally,  however,  this  is  not  the  case.  Under  any 
circumstances,  however,  these  premonitory  symptoms  may  make  it  difficult 
properly  to  interpret  the  underlying  condition.  Not  infrequently  these  pro- 
dromal symptoms,  previously  quite  unintelligible  to  the  physician,  are  at  once 
explained  by  the  sudden  appearance  of  an  attack  of  gout.  Similar  to  the-,' 
premonitory  symptoms  are  the  pathologic  phenomena  which  have  been  desig- 
nated by  nie  a-  intermediate  symptoms.  They  occur  in  the  intervals  between 
the  attacks  of  gout,  -how  remarkable  similarity  to  the  premonitory  symptoms, 
hut  are  much  more  difficult  to  e\])lainras  the  preceding  gouty  paroxysms  have 
closed  the  path  to  their  proper  recognition.  YVe  shall  later  consider  more 
minutely  these  premonitory  and  intermediate  symptoms.  It  appears  expedient 
first  to  direct  attention  to  the  typical  condition  in  primary  arthritic  gout, 
namely,  to  the  acute  paroxysm  of  gout,  the  typical  attack. 

The  clinical  hi-tory  of  the  physician  suffering  from  primary  arthritic  gout 
(Observation  I)  shows  that  the  first  attack  of  gout  may  occur  in  very  early 
life.  I  shall  later  demonstrate  that  this  i-  also  true  of  the  appearance  of 
extensive  gouty  tophi.  A-  a  ride,  however,  this  is  not  the  case.  The  first 
typical  attack  id' gout  usually  occurs  shortly  before  or  after  the  fortieth  year 
of  life.  The  gouty  attacks  frequently  recur  at  certain  Beasons  of  the  year. 
especially  at  the  beginning  of  Bpring  ami  at  the  beginning  of  winter.  Besides 
certain  premonitory  symptoms,  the  true  attack  may  he  preceded  by  prodromes 
in  the  part  of  the  body  that  is  to  he  the  seat  of  the  paroxysm,  such  as  drawing 
pains,  or  slightly  disagreeable  sensations  to  which  the  patient  pays  no  atten- 
tion, and  of  which  we  only  learn  by  careful  questioning.  Much  more  fre- 
quently the  attack-  begin  Buddenly,  often  coming  like  a  thief  in  the  night, 
and  surprising  the  calm  sleeper.  As  a  rule,  the  first  attack-  are  prone  to  be 
localized  in  the  most   peripherally  situated  part-  of  the  body,  am!  especially 

in    the   joint-   of    the    lower   extremities.      The    joint-    of    the    feet,    chiefly    the 

first  metatarsophalangeal  joint-,  are  most  frequently  attacked.  The  typical 
attack  of  -um  i-  a  more  or  less  severe  process  characterized  by  an  inflamma- 


134  GOUT 

tory  but  aseptic  course,  which  is  strikingly  similar  to  an  erysipelatous  inflam- 
mation. Corresponding  to  the  intensity  of  the  inflammatory  process,  there 
is  as  a  rule  extraordinarily  severe  pain.  Most  patients  declare  it  to  be  as 
though  the  affected  parts  of  the  body  were  tightly  screwed  in  a  vise.  The 
skin  is  intensely  red  (purplish  red  or  bluish  red),  sometimes  even  permeated 
by  small  hemorrhages;  it  appears  as  though  suppuration  were  developing,  and 
is  tender  on  pressure,  glistening,  and  swollen.  The  swelling  is  the  consequence 
of  edema;  upon  pressure  there  is  pitting  of  the  skin  which  only  very  slowly 
disappears  when  the  pressure  is  relaxed.  In  the  most  severe  cases  active 
motion  is  impossible,  and  upon  attempting  passive  movement  of  the  painful 
joints,  the  patients  resiot.  Under  these  circumstances,  the  patient  is  early 
confined  to  his  bed. 

Apart  from  these  local  pathologic  phenomena,  we  also  observe  in  acute 
paroxysms  of  gout  disturbances  of  the  general  constitution.  Especially  note- 
worthy are  the  fever  and  the  symptoms  dependent  upon  this.  In  the  milder 
attacks,  fever  may  be  absent.  We  note  from  Observation  I  that,  in  the  same 
individual,  it  was  present  in  some  attacks  and  absent  in  others.  Occasionally 
there  is  a  slight  rise  of  temperature  only  in  the  first  days,  so  that  if  the  patient, 
for  instance,  comes  under  observation  only  upon  the  third  day  of  the  attack 
there  may  be  no  fever.  Usually,  the  fever  is  moderate,  a  rise  above  102.2°  F. 
being  rarely  reached  at  the  height  of  the  paroxysm.  During  the  exacerbations 
so  frequently  observed  in  attacks  of  gout,  the  temperature  rarely  exceeds 
101.3°  F.,  and  when  remission  occurs,  as  a  rule  it  at  once  falls  to  normal. 
The  age  of  the  patient  seems  to  have  some  influence  upon  the  temperature 
curve  during  the  paroxysm,  as,  under  otherwise  similar  conditions,  the  highest 
temperatures  occur  in  young  robust  patients.  Nevertheless,  in  the  aged,  dur- 
ing acute  attacks,  rises  in  temperature  are  by  no  means  absent. 

The  further  course  of  the  gouty  inflammation  in  the  affected  part  of  the 
body  is  generally  typical.  After  the  para-articular  phlegmons  have  existed  for 
a  few  days,  or  several  weeks  and  longer  with  remissions  and  exacerbations,  the 
latter  being  sometimes  so  severe  that  an  extensive  joint  suppuration  seems 
imminent,  the  inflammatory  symptoms  ameliorate,  the  pain  usually  subsides, 
and  the  affected  joint  in  many  cases  returns  apparently  to  its  normal  condi- 
tion. As  in  erysipelas,  the  skin  becomes  pale  and  desquamates.  Neverthe- 
less, decided  sensitiveness  to  pressure  may  be  noted  in  the  affected  joints,  and 
this  increases  upon  active  and  passive  movement. 

As  a  rule,  the  first  attacks  of  gout  are  limited  to  one  or  several  small  joints 
of  an  extremity;  rarely,  for  example,  is  the  knee-joint  implicated  in  the  first 
attack  of  gout.  Effusions,  which  are  not  at  all  rare  in  the  gouty  paroxysm, 
localize  usually  in  the  joints,  and  often  they  last  for  a  long  time.  This  causes 
the  condition  so  frequently  noted  in  the  later  course  of  the  gouty  process,  in 
which  two  or  more  joints  are  attacked,  one  after  the  other,  and  thus  the  par- 
oxysm is  decidedly  prolonged.  An  illustration  of  this  and  of  the  fact  that  in 
the  course  of  gout  numerous  joints  are  always  implicated  may  here  be  given. 

Observation  II. — X.,  a  lawyer  from  B.,  forty-six  years  of  age,  consulted  me  on  the 
6th  of  July,  1896,  on  account  of  pout.  His  father — now  over  eighty  years  of  age — and 
his  younger  brother  are  both  said  to  have  had  an  attack  of  pout.     His  mother  died  at 


SYMPTOMATOLOGY  135 

the  age  of  fifty-six  of  diabetes  mellitus.  The  patient  previously  had  two  attacks  of 
pyorrhea.  He  admits  prior  and  occasional  marked  abuse  of  alcohol;  since  practising 
his  profession  he  drinks  moderately.  He  has  always  been  ;i  great  eater,  and  takes  but 
little  exercise.  At  the  age  of  twenty-one  or  twenty-two  he  had  a  Blight  attack  of  gout 
in  a  joint.  The  attack  came  on  suddenly  at  five  o'clock  in  the  afternoon  while  in  his 
office.  In  the  following  June  the  first  severe  attack  occurred,  and  confined  him  for 
almost  three  months  to  his  room.  Remedies — external  and  internal — were  ineffectual 
until  finally  the  Ann  run,)  remedy  I  ?) — potassium  iodid.  Colchicum  and  colocynthitin — 
brought  relief.  The  attack  was  in  the  left  foot,  and  localized  especially  to  the  greal  toe. 
The  paroxysms  now  recurred  yearly,  and  the  right  foot  also  became  implicated.  In  the 
year  1888,  after  a  prolonged,  exhausting  ride  upon  the  tricycle,  an  attack  of  gout 
occurred  which  was  localized  in  the  left  knee-joint.  In  November.  1  s !>.""» .  a  seven-  attack 
of  gout  came  on  after  drinking  a  somewhat  larger  quantity  than  usual  of  cognac  with 
which  the  patient  hoped  to  abort  an  attack  of  influenza,  At  first  both  feet  and  the 
knee-joints  were  implicated;  the  patient  was  compelled  for  almosl  five  months  to  remain 
uninterruptedly  in  tin-  recumbenl  posture.  Relapses  constantly  occurred  in  which  also 
the  right  elbow  -joint  was  involved.  He  report-  that,  when  free  from  attack-,  the  urine 
was  dark  and  frequently  contained  sediment.  The  patient  was  under  observation  in  my 
private  hospital  from  the  6th  to  the  13th  of  July.  Tie  had  tophi  in  the  concha  auris. 
The  daily  excretion  of  urine  upon  a  mixed  die!  amounted  to  0.6-0.8  gram  in  twenty- 
four  hours  with  an  excretion  of  area  of  about  4<>  grams  and  a  phosphate  excretion  of 
from  3.1-2. '.I  grams.  I  regulated  the  diel  and  advised  him  to  spend  his  .summer  in  the 
Tyrol  or  in  Switzerland.  lb  did  the  latter,  in  the  main,  the  patient  apparently  fol- 
lowed directions.  That  he  rigidly  adhered  t « »  the  diet,  and  absolutely  avoided  alcohol, 
cannot,  however,  be  asserted.  The  besl  proof  of  this  is  furnished  by  the  reappearance 
of  gouty  paroxysms.  In  the  first  year  during  which  he  adhered  to  the  dietetic  regime, 
he  had  no  attacks. 

I  cannot  enter  into  details  here:  the  following  fact  will  suffice.  When  the  patient 
celebrated  his  fiftieth  birthday,  he  thought  he  could  oof  do  without  champagne.  1  know 
not  how  much  he  drank,  but  this  I  do  know,  that  the  patient  had  a  very  severe  paroxysm 
of  gout  upon  the  following  day. 

The  following  case  also  is  Instructive.  It  proves  that  persons  with  a  gouty 
predisposition  can.  by  a  proper  mode  of  life,  keep  the  disease  in  check.  If  they 
fail  to  <lo  it,  not  only  may  severe  attacks  of  goul  appear  in  rapid  sequence, 
hut  it  is  occasionally  observed  thai  the  paroxysms  sunn  attack  a  greater  number 
of  joints. 

Observation  111. — The  Commercial  Councilor  and  City  Councilman,  X.  aged  forty- 
nine,  a   very  busy  man.  whose  grandfather  Buffered  greatly   from  gout,  state-  that   he 

come-   from  a    family   in   the  main   very   healthy.      Toward   the  end  of   the  -ixth   decade  of 

the  last  century,  he  had  Asiatic  cholera  in  Vienna;  as  a  young  man  he  had  a  Bevere 
attack  of  gonorrhea.  The  patient  was  under  observation  in  my  private  hospital  from 
the  I lth  to  the  1  tili  of  August,  1899.  Regarding  his  gout  the  patient  wrote  for  me  the 
following  history:  "About  six  years  ago  I  was  attacked  with  gout}  pain-  in  the  great 
toe,  which  appealed  every  -ix  iiimith-  and  very  rapidly  passed  away.  I  went  to  Kissingen 
every  year,  which  benefited  mi  greatly.  Last  yeai  L898)  I  had  a  very  painful  attack 
it  in  the  foot,  particularly  in  the  small  joints,  and  in  September,  1898,  I  went  to 
Wiesbaden.  At  the  beginning  of  February  <u'  the  following  year  (1899]  another  and 
al-o  very  severe  attack  of  '_r"ut  occurred,  mainly  in  the  right  knee,  but  also  in  the  small 

joints  of  the  right  foot,  which  kept  me  confined  to  bed  for  about  three  week-.  In  May. 
1899,    I    went    to    Aix   la  (   hapelle.    where    I    took    the    bath    cure    for    four    Week-,    and    U-ed 

douche-.  Shortly  after  my  return,  gouty  pains  recurred,  but  disappeared  in  a  few  days. 
At  the  present  time,  upon  prolonged  -ittinLr.  slight  pains  occur  in  the  joints  of  the  right 
foot  but  -'"in  pass  away."  This  closes  the  report.  The  patieut  had  gouty  tophi  in  the 
right  ear.  The  urine  -bowed  a  trace  <>f  albumin.  The  intestines  appeared  t.i  be  filled 
with  feces.     The  gout)   joints  were  sensitive  t<>  pressure.    The  patient   relate-  that   the 


136  GOUT 

attacks  constantly  appear,  and  so  suddenly  and  so  decidedly  that  even  ten  minutes  after 
the  onset  of  an  attack  he  is  unable  to  walk.  Lately  the  patient  has  suffered  from 
cramps  in  the  calves.  His  nutrition  is  good.  He  is  extremely  excitable,  and  lives  in 
constant  dread  of  the  appearance  of  a  sudden  attack.  The  patient  tells  me  that  the 
liqueur  Laville  helps  him,  and  purges  him  decidedly.  I  ordered  the  observance  of  purely 
dietetic  rules,  and  upon  the  7th  of  March,  1000.  lie  wrote  to  me  that  he  was  adhering 
to  my  regulations,  and  since  that  time  he  has  had  no  attack  of  gout.  Nevertheless,  I 
have  reason  to  believe  that  the  patient  will  not  long  continue  this  mode  of  life,  although 
it  is  beneficial  to  him. 

In  regard  to  the  gouty  paroxysms  and  the  relative  frequency  with  which 
the  individual  joints  are  attacked  by  the  gouty  process,  what  has  already  been 
stated  may  be  amplified  by  the  following  account.  The  joints  of  the  knee, 
elbow,  and  vertebra  are  far  less  frequently  attacked  than  the  joints  of  the 
toes  and  the  tarsal  joint,  but  among  these  rarer  localizations  that  of  the  knee- 
joint  is  perhaps  the  most  frequent.  I  once  saw  in  a  patient  aged  fifty-four, 
after  all  the  peripheral  joints  had  been  attacked  by  gouty  paroxysms,  an  acute 
gouty  inflammation  of  the  left  sternoclavicular  joint.  Any  joint  may  be 
attacked  by  gout ; '  even  the  small  joints  of  the  larynx  have  been  found  in- 
volved. This  much  is  evidently  certain,  that  gouty  changes  in  the  joints  of 
the  legs  are  not  only  earlier  but  also  far  more  common  than  in  the  joints  of 
the  upper  extremities.  The  joints  of  the  hand  and  of  the  elbow  are  as  a  rule 
simultaneously  involved.  The  premonitory  as  well  as  intermediate  symptoms, 
to  be  discussed  later,  may  become  aggravated  with  the  appearance  of  an  acute 
paroxysm  of  gout. 

In  connection  with  this  description  of  an  acute  attack  of  gout  it  appears 
necessary  to  say  a  few  words  in  regard  to  the  composition  of  the  urine,  espe- 
cially as  to  the  excretion  of  uric  acid.  Garrod  assumed  that  during  the  acute 
attack  the  amount  of  uric  acid  excreted  was  diminished.  He  considered  this 
to  be  due  to  a  functional  disturbance  of  renal  activity,  apparently  because  he 
was  unable  to  find  material  changes  in  the  kidneys.  This  diminished  excre- 
tion of  uric  acid  led  Garrod,  as  already  stated,  to  believe  the  gouty  attack 
due  to  a  retention  of  uric  acid  in  the  body,  i.  e.,  a  generalized  uric  acid 
stasis.  Garrod's  view  is  vulnerable  from  more  than  one  point.  It  must  be  first 
stated  that  a  product  of  metabolism  which  may  be  still  further  decomposed 
in  the  body  may,  during  this  further  decomposition,  appear  in  diminished 
amounts  in  the  urine;  hence  it  cannot  be  concluded  from  its  lessened  excre- 
tion in  the  urine  that  it  is  also  produced  in  diminished  amount  in  the 
organism.  Furthermore,  if  the  view  of  Garrod  were  actually  correct,  it  is 
incomprehensible  why — as  in  the  majority  of  cases — the  attack  of  gout  should 
be  localized  in  the  metatarsophalangeal  joint  of  the  great  toe.  Now,  however, 
since  the  old,  quite  untrustworthy  methods  of  estimating  uric  acid  in  the 
urine  have  been  replaced  by  reliable  ones,  it  has  been  demonstrated  not  only 
that  the  amount  of  uric  acid  excreted  during  an  attack  of  gout  is  not  decreased 
but  that  it  is  either  normal  or  decidedly  increased.  It  is  by  no  means  necessary 
that  uric  acid  sediment  or  urate  sediments  should  be  found  in  the  urine.  An 
increased  excretion  of  uric  acid  during  an  attack  of  gout  is  in  the  main  due 
only  to  the  attack  itself.  It  has  been  shown  to  be  independent  of  the  nature 
of  the  food  and  of  the  total  albumin  metabolism.     Thus  the  view  expressed 


SYMPTOMATOLOGY  137 

above  gains  support  from  the  fact  that,  in  the  gouty  process,  an  increased 
production  of  uric  acid  occurs,  and  plays  an  important  role.  In  the  cases  of 
gout  complicated  with  severe  renal  inflammation  the  complete  retention  of 
the  excretory  function  of  the  kidney  for  uric  acid  is  proven  beyond  doubt  by 
the  fact  that,  on  the  administration  of  food  rich  in  nuclein,  the  amount  of 
uric  acid  in  the  urine  of  such  persons  may  be  increased. 

Associated  with  typical  attacks  of  gout  and  occasionally  without  such 
attacks  having  preceded,  in  a  certain  proportion  of  gouty  patients  deposits  of 
crystals  which  consist  of  acid  sodium  urate  take  place  in  the  tissues.  These 
prove  that  we  are  dealing  with  gout.  Most  frequently  they  are  found  in  the 
joints  in  which  one  or  more  attacks  of  gout  have  occurred,  and  most  commonly 
in  the  first  metatarsophalangeal  joint,  in  which  the  first  and  the  most  fre- 
quent paroxysms  of  gout  are  localized.  However,  it  sometimes  happens  that 
these  deposits  are  absent  even  when  many  typical  attacks  of  gout  have  pre- 
ceded. A  prerequisite  for  the  production  of  such  urate  deposits  is  tissue 
necrosis  in  the  affected  parts  of  the  body.  If  the  deposit  of  urate  in  the  tissue 
occur-  in  a  nodular  form,  gout  ffODUL?s  (tophi)  are  spoken  of.  The  number 
of  these  in  the  same  individual  may  be  quite  large.  The  size  of  the  tophi 
varies  decidedly;  small  at  the  beginning,  they  may  attain  the  size  of  a  chestnut 
or  even  become  larger.  The  analysis  of  two  gouty  nodules  in  the  laboratory 
of  my  clinic  shows  thai  the  first  consisted  mainly  of  uric  acid  (59.7  per  cent.) 
and  alkalies  which  formed  urates  with  it  (nearly  70  per  cent.).  These  urates 
arc  to  be  looked  ujm.h  as  monosodium  urates  (Tollens),  though  Roberts  d< 
nates  them  as  biurates.  There  is  also  about  28  per  cent,  of  animal  matter 
present.  Phosphoric  acid,  calcium  and  magnesium — all  three  in  combination 
— were  pr<  -cut  only  in  trace-.  The  analysis  of  the  second  gouty  tophus  showed 
in  the  main  analogous  condition-.  Here  also  uric  acid  made  up  the  highest 
percentage  (öl^  per  cent.):  -odium  oxid  gave  L2.28  percent.,  and  animal 
matter  26.45  per  cent.  For  the  practitioner,  of  course,  these  gouty  tophi 
which  are  easily  found  and  unquestionable  are  of  chief  interest  from  their 
diagnostic  value.  No  error  in  diagnosis  can  be  made  in  the  case  of  a  gouty 
patient  with  tophi  in  the  ear.  where  they  not  infrequently  develop  in  -real 
numbers.  Gouty  tophi  may.  however,  develop  at  very  differenl  part-  of  the 
body.  The  bursas  mucosa  which  are  usually  implicated  in  primary  arthritic 
gout,  and  which  are  very  frequently  filled  with  urate  containing  material,  he- 
come  the  seal  of  such  tophi.  Every  fresh  gouty  inflammation  which  is  localized 
there,  as  a  rule,  produces  a  paroxysmal  increase  of  the  tophus.  The  bursa 
over  the  olecranon  process  appear-  to  be  the  preferred  -eat  of  such  gouty  con- 
cretions. Mere  in  some  patient-  the  lir-t  gouty  tophus  develops.  These  oratio 
deposits  sometimes  form  without  pain.  There  i- at  lir-t  swelling  from  which, 
upon  puncture,  a  white  cream-like  fluid  consisting  of  acid  -odium  urate  exudes. 
hater  these  tophi  become  hard  and  firm.  They  may  disintegrate,  and  form 
gouty  ulcers,  the  base  of  which  is  the  previously  mentioned  urate-.  The  ulcers 
are  slow  in  healing  and  may.  according  to  their  localization,  etc.,  lead  to  Beri- 
0118  consequences  when  suppuration  develops.  Even  when  the  urate  masses  sep- 
arate and  the  ulcer-  finally  heal,  they  -how  a  constant  tendency  to  again  form. 
To  illustrate  the  clinical  history  of  gouty  tophi  some  cases  may  be  quoted: 


138  GOUT 

Observation  IV. — This  record  shows  what  I  have  already  emphatically  stated  that, 
in  comparatively  young  persons  who  are  attacked  by  primary  arthritic  gout,  an  extensive 
tophus  formation  may  occur.  This  patient  was  a  merchant,  aged  twenty-five,  from 
Cleveland  (Ohio),  who  was  evidently  always  a  great  eater,  whereas  he  took  scarcely  any 
alcohol,  nor  was  there  any  family  predisposition.  Even  in  his  tenth  year  the  patient 
suffered  from  decided  cramps  in  the  calves,  and  in  his  sixteenth  year  he  had  an  attack 
of  gout  in  the  first  left  metatarsophalangeal  joint.  These  attacks  recurred  frequently, 
and  as  time  passed  the  intervals  became  shorter.  In  these  paroxysms  not  only  the  various 
small  but  also  the  large  joints,  occasionally  several  simultaneously,  were  involved.  The 
severest  attacks  always  occurred  in  spring  and  late  autumn.  About  a  year  and  a  half 
after  the  first  attack — in  the  patient's  eighteenth  year — the  first  gouty  tophi  appeared 
in  the  left  ear.  The  paroxysms  almost  always  came  on  suddenly;  only  rarely  were 
drawing  pains  in  the  joints  present  as  prodromes,  and  in  these  joints  the  attack  was 
usually  localized.  Psychical  disturbance  was  said  to  favor  the  appearance  of  the 
attacks.  I  saw  the  patient  for  the  first  time  upon  September  29,  1S85.  He  weighed  124 
pounds.  His  weight  is  said  to  have  never  been  greater  than  this.  He  was  a  pale,  medium- 
sized  man  and  had  a  large  number  of  gouty  tophi  in  both  ears.  The  third  phalanx  of 
the  little  finger  of  the  left  hand  was  thickened  to  more  than  double  its  size  in  conse- 
quence of  gouty  deposits.  Gouty  swellings  were  also  found  in  several  of  the  other  joints 
of  the  finger.  Between  the  first  and  second  phalanges  of  the  middle  finger  there  was  an 
extensor  tendon  with  a  movable,  indolent  gouty  nodule.  A  somewhat  smaller  one  was 
situated  upon  the  radial  side  of  the  left  index  finger.  Tophi  were  absent  upon  the  right 
hand.  Upon  the  third  toe  of  the  right  foot  a  tophus  about  the  size  of  a  hazelnut  was 
present.  Upon  the  left  foot  there  were  two  nodules  which  had  ruptured.  One  of  these 
gouty  ulcers  was  situated  upon  the  nail  phalanx  of  the  great  toe,  the  other  at  the  heel. 
The  skin  surrounding  these  ulcers  was  inflamed.  Where  these  gout  tophi  had  ruptured, 
white,  chalky,  urate  masses  exuded.  About  fourteen  days  after  the  rupture  of  the 
tophus  at  the  heel,  almost  all  of  the  urate  masses  had  been  discharged.  In  the  large 
joints  no  tophi  were  to  be  seen,  nor  were  any  deformities  noted.  The  appetite  of  the 
patient  continued  good;  the  bowels  were  regular.  About  September  20,  1885,  nine  days 
before  the  patient  came  under  my  observation,  he  had  an  acute  attack,  running  an 
afebrile  course,  not  accompanied  by  disturbance  of  the  appetite  nor  of  the  general  system 
and  localized  in  the  left  heel,  the  fingers  of  the  right  hand,  and  the  right  elbow-joint; 
amelioration  began  upon  the  6th  of  October.  The  internal  organs  of  the  patient  were 
normal  and  he  was  by  no  means  cachectic.  The  urine  did  not  contain  albumin  nor  sugar. 
The  daily  excretion  of  urea  at  the  height  of  the  last  mentioned  attack  varied  between 
23.3  and  27.1  grams  in  twenty-four  hours.  The  uric  acid  estimations,  at  that  time 
made  by  Heintz's  method,  can  no  longer  be  utilized.  The  examination  of  the  sweat  of 
the  patient  by  means  of  the  murexid  test  for  uric  acid  gave  a  brown  color  with  nitric 
acid,  which  upon  the  addition  of  ammonium  changed  to  a  yellowish  brown.  In  the 
following  winter,  in  Abbazia,  the  patient  had  an  attack  of  gout  which  lasted  for  two 
weeks.  In  connection  with  this  a  gouty  tophus  developed  upon  the  flexor  side  of  the 
second  phalanx  of  the  ring  finger  of  the  right  hand  which  the  patient  showed  to  me 
when  he  consulted  me  in  the  following  May.  After  a  stay  in  Abbazia,  he  also  went  to 
other  places  in  Italy,  and  although  he  had  no  further  attacks  of  gout  he  felt  by  no 
means  well. 

We  see  in  this  observation  a  case  of  primary  arthritic  gout  which  began 
early  in  life;  paroxysms  rapidly  succeeded  each  other  and  very  soon  led  to 
quite  extensive  tophus  formation. 

Gout  shows  a  varying  course.  In  regard  to  the  paroxysm,  it  must  be 
emphasized  here  that  with  a  slight  gouty  predisposition  combined  with  a  suit- 
able manner  of  life,  the  typical  attacks  occur  only  rarely  and  pursue  a  short 
and  mild  course.  Attacks  of  gout  which  are  of  rare  occurrence  may  assume 
a  definite  periodic  type.  I  knew  an  army  officer  of  high  rank  who  lived  to 
be  over  eighty  years  of  age,  and  who,  up  to  the  time  of  his  death,  had  each 


SYMPTOMATOLOGY  139 

year  an  attack  of  gout.  People  with  Blight  gouty  predisposition,  in  whom 
gout  develops  under  the  influence  of  one  or  more  favoring  factors,  may  keep 
the  disease  in  cheek  provided  these  predisposing  factors  are  removed.  Thus, 
for  example,  if  the  patient  modifies  his  mode  of  life  he  may  conquer  the 
existing  pathological  predisposition  which  would  otherwise  enslave  him.  If 
such  persons  have  been  exempt  from  gout  for  a  longer  period  than  usual,  they 
flatter  themselves  that  they  have  been  permanently  cured  of  gout,  although 
the  physician  may  have  frequently  cautioned  them  to  the  contrary;  but  they 
learn  only  too  soon,  if  they  return  to  their  former  manner  of  life,  that  this 
is  by  no  means  the  case.  A  single  excess  is  sufficient  to  reawaken  the  slumber- 
ing predisposition  to  the  disease. 

We  now  turn  to  the  description  of  the  premonitory  and  intermediate 
symptoms  by  which,  as  already  remarked,  1  desire  to  have  understood  those 
symptoms  which  precede  the  individual  paroxysms  or  are  present  between 
the  attack-.  When  the  individual  attacks  of  gout  have  passed  off,  and  during 
the  period  free  from  attack-,  gouty  patients  are  often  troubled  with  a  number 
of  ailments.  I  shall  here  exclude  entirely  those  symptoms  which  are  due  to 
the  implication  of  the  internal  organs,  and  also  others  which  not  rarely  com- 
plicate the  pathological  process;  of  these  I  shall  speak  later.  In  the  period 
free  from  attacks,  there  is  often  more  or  less  decided  discomfort,  referred 
particularly  to  the  joints  which  have  been  affected,  but  also  to  those  nol 
attacked  in  the  paroxysms;  these  disturbances  often  affect  the  muscles  and 
bones  of  the  surrounding  areas.  We  must  especially  mention  here  that  there 
is  sometimes  marked  sensitiveness  to  pressure  in  the  periosteum;  tin-  is 
elicited  by  pressure  of  the  skin  covering  the  bones,  particularly  the  superficial 
bones  such  as  the  shin,  but  also  the  sternum,  and  more  often  the  ribs.  More 
troublesome,  because  often  acute  and  ushered  in  with  great  severity,  are  the 
muscular  symptoms,  especially  the  painful  oramps  in  II"'  legs  which  recur  fre- 
quently; no  less  unpleasant  are  the  so-called  rheumatic  pains  in  the  lumbar 
region  called  by  the  Germans  ".Hexenschuss"  popularly  known  in  English  as 
••  crick  in  lh<-  bach."  To  this  may  he  added  vague,  wandering,  muscular  pains 
and  a  sensation  of  extreme  fatigue  which  have  a  particularly  depressing  effeci 
upon  the  patient.  Although  these  muscular  Bymptoms  are  by  no  means 
pathognomonic  of  goul — for  we  observe  analogous  symptoms  occasionally  also 
in  diabetes — they  have,  aotwithstanding,  a  certain  diagnostic  value.  Between 
Lr"Ut.  diabetes  mellitus  and  obesity,  there  are  intimate  relationships.  1  have 
included  these  three  diseases  in  a  pathologic  -roup  a-  "general  diseases  <>f  the 
protoplasm  with  u  hereditary  predisposition"1 

Similar  to  the  intermediate  Bymptoms  are  those  which  precede  the  attacks. 
These  may  exist  for  year-  before  the  outbreak  of  a  paroxysm.  According  to 
my  experience.  - 1 1 « - 1 1  symptoms  may  be  presenl  in  per-. ui-  with  slight  gouty 
predisposition  who  are  of  active  habits  and  live  temperately;  they  remain  the 
only  indication  of  the  affection  and  a  gouty  paroxysm  never  appears. 

It  i-  obvious  that  premonitory  and  intermediate  Bymptoms  may  also  occur. 

i  Ihn/sein  mill.  Wochenschr.,  IS'IS.  Nr.  II.  und  Verhandlungen  der  deutschen  Natur- 
forscher  und  Aerzte,  70;  Versammlung,  ~.  Hälfte,  Leipzig,  1899,  p.  7:. 


140  GOUT 

soon  or  late,  in  consequence  of  implication  of  the  internal  organs  in  the  gouty 
process,  for,  in  primary  arthritic  gout,  as  already  explained,  the  entire  organ- 
ism is  more  or  less  damaged  in  the  course  of  time.  These  deleterious  effects 
will  show  themselves  earliest  in  persons  whose  gouty  predisposition  is  severest 
and  in  those  who  are  most  exposed  to  the  exciting  causes  of  the  disease.  The 
acutest  cases,  however,  are  those  in  which  several  auxiliary  causes  become  active 
in  combination  with  a  decidedly  gouty  predisposition.  Under  such  circum- 
stances it  may  rapidly  become  apparent  that,  as  is  true  also  in  primary  arthritic 
gout,  "  Totum  corpus  est  podagra," 

This  leads  us  to  the  discussion  of  so-called  visceral  gout.  This  indicates 
nothing  else  than  the  implication  of  various  other  tissues  and  organs  in  the 
gouty  process.  In  gout  there  is  a  decided  tendency  to  catarrhal  inflammation 
of  the  mucous  membrane,  and  perhaps  of  the  digestive  canal,  while  even  with- 
out this,  many  gouty  patients  throw  too  much  labor  upon  their  digestive 
organs,  by  immoderate  eating  and  drinking,  thus  exposing  them  to  inflamma- 
tory affections  of  this  nature.  We  may  mention,  in  passing,  the  frequent 
catarrhal  affections  of  the  mouth  and  pharynx  in  gout.  The  tongue,  too,  often 
take-  part  in  this.  Among  the  etiological  factors  in  so-called  psoriasis  lingua', 
gout  must  be  included.  Worthy  of  note  in  the  gouty  is  the  loosening  of  the 
teeth  which  is  often  observed,  and  terminates  in  their  premature  falling  out; 
an  alveolar  periostitis  is  looked  upon  as  the  essential  cause  of  this  very  dis- 
agreeable symptom.  Naturally  the  stomach  is  early  implicated  in  gout,  and 
it  has  been  quite  properly  said  that  the  stomach  is  in  gout  what  the  heart  is 
in  rheumatism.  The  gastric  dyspepsias  of  the  gouty  play  a  great  role  in  tbe 
symptomatology,  even  in  those  cases  in  which  special  dietetic  errors  cannot  be 
proven.  The  causes  of  these  dyspepsias  are  manifold  as  has  been  demonstrated 
by  recent  investigations.  In  the  paroxysms  of  gout  a  decreased  motility  of 
the  stomach  and  a  decided  diminution  of  the  degree  of  acidity  of  the  gastric 
juice  has  been  observed;  a  deficiency  in  HCl  is  said  to  be  especially  common. 
It  is  certainly  true  that  in  gouty  patients  dyspeptic  symptoms  of  all  kinds, 
among  which  anorexia  is  perhaps  in  the  front  rank,  are  wont  to  appear.  Just 
as  frequent  in  gout  are  intestinal  dyspepsias.  Often  in  this  condition  we 
observe  very  troublesome  and  obstinate  constipation,  by  the  removal  of  which, 
after  treatment  of  the  stomach  has  been  quite  ineffectual,  in  many  cases  the 
gastric  dyspeptic  symptoms  entirely  disappear  and  even  the  symptoms  of  gout 
in  the  extremities  are  decidedly  improved.  To  the  symptoms  in  primary 
arthritic  gout  referred  to  the  digestive  canal,  we  may  add  that  in  this  condition 
also  functional  disturbances  of  the  activity  of  the  liver  are  noted.  That  inti- 
mate co-relation  exists  between  gout  and  the  liver  can  hardly  be  doubted. 
Charcot  and  others  have  even  looked  upon  gout  as  the  result  of  a  functional 
disturbance  of  the  liver.  However,  it  is  not  the  purpose  of  this  article  to  enter 
upon  the  discussion  of  these  complicated  and  theoretic  questions.  On  the 
other  hand,  the  practical  and  important  point  in  treatment  is  to  be  empha- 
sized, that  primary  arthritic  goal  and  cholelithiasis  occur  simultaneously  with 
comparative  frequency.  Among  other  factors,  the  predisposition  in  gout  of 
the  mucous  membrane  of  the  biliary  passages  to  inflammatory  processes  analo- 
gous to  that  of  other  mucous  membranes  may  represent  an  important  link  in 


SYMPTOMATOLOGY  141 

the  chain  connecting  these  pathologic  processes.  It  may  ho  here  mention«-.! 
that  in  the  etiology  of  the  so-called  hypertrophic  hepatic  cirrhosis  gout  appar- 
ently plays  a  part;  indeed  the  liver  appears  to  he  implicated  in  primary 
arthritic  gout,  and  even  more  frequently  than  is  usually  assumed. 

However,  the  heart  and  the  vascular  system  play  a  far  more  important  role 
in  gout  than  the  liver,  at  least  from  the  standpoint  of  the  practitioner. 

In  regard  to  the  heart,  it  may  be  remarked  that  in  primary  arthritic  gout 
functional  disturbances  occur  frequently;  such  are  palpitation,  intermittent 
beats,  arrhythmia,  and  other  irregularities  of  the  heart's  action,  decided  pain  in 
the  precordia,  etc.  These  occur  mostly  as  prodromal  or  intermediate  symp- 
toms, and  as  a  rule  diminish  with  the  development  of  the  gouty  paroxysm. 
In  general,  they  are  not  of  serious  import,  and  are  often  mild  and  transitory; 
nevertheless,  they  are  frequently  distressing  to  the  patient.  I  have  often 
observed  such  prodromal  symptoms  in  gouty  patients  combined  with  stubborn 
intestinal  disturbances,  principally  obstinate  constipation,  and  have  seen  the 
cardiac  symptoms  disappear  with  a  proper  evacuation  of  the  bowels  after  large 
enemata  of  oil.  These  functional  cardiac  disturbances  which  .l.-velop  in  pri- 
mary arthritic  goul  are  usually  observed  in  persons  under  fifty  years  of  age. 
In  older  persons,  especially  in  such  as  have  had  a  number  of  severe  attacks  of 
gout,  we  should  bear  in  mind  that  these  symptoms  are  caused  by  organic 
changes  in  the  circulatory  apparatus,  even  though  by  physical  examination 
no  gross  disturbance  can  be  determined.  I  am  very  careful  not  to  say  in  such 
cases  "The  heart  is  normal,"  but  content  myself  with  the  expression:  "  I  can 
find  nothing  abnormal  in  the  heart."  Particularly  serious  in  such  cases  are 
attacks  of  angina  pectoris,  although  I  know  quite  a  number  of  gouty  patients 
who.  in  spite  of  this,  have  lived  for  a  long  time.  In  the  case  of  older  gouty 
patients,  especially  those  who  suffer  from  attack--  of  angina  pectoris,  there  is 
often  disease  of  the  coronary  arteries.  In  fact  we  Bee,  a-  the  result  of  gout, 
all  the  different  pact-  of  the  heart  (myocardium,  endocardium,  valves,  peri- 
cardium?) attacked,  sometimes  singly,  sometimes  in  combination.  Occasion- 
ally, deposits  of  urates  have  been  found  in  the  excrescences  of  the  cardiac  \. 
and  in  so-called  o  ion  of  the  aorta.     Apart  from  these  cardiac  di-turb- 

ances,  there  i-  ;d-<>  gouty  renal  inflammation  which  occurs  in  primary  arthritic 
goul  after  a  longer  or  -hortet-  time,  and  I  -hall  revert  to  this  later.  There 
are  no  specific  cardiac  Bymptoms  of  gout:  nevertheless,  when  investigating  the 
etiology  of  attacks  of  angina  pectoris,  we  should  in  the  first  place  think  of 
gout.  How  a  cardiac  affection  can  arise  upon  a  gouty  basis  may  perhaps  he 
understood  from  the  etiology.  We  can  readily  understand  that,  in  the  course 
of  primary  arthritic  gout,  the  hear!  as  well  ;t-  the  vascular  system  mu-t  become 

damaged  because  the  organ-  of  circulation  are  overwhelmed   with  blood   laden 

with  urates  which  do  them  injury.    In  the  arteries,  under  these  circumstances, 
there  is  developed  a  chronic  inflammatory  process,  atheroma  or  an  endarteritis; 
and  phlebectases  mu-t  also  he  explained  in  the  same  manner.  ;it  least  in  part. 
Frequently  disease  of  the  urinary  organs  develops  in  tin-  course  of  primary 

arthritic   Lrout.      I    refer   in    the   first    place  to   the  complication   of   Lr"ut    with 

nephrolithiasis.    This  latter  association  ha-  been  denied  by  some,  but  in. -or- 

rectly;  by  other-  it   i-  declared  to  he  a  mere  coincidence.     But  here,  in  my 


142  GOUT 

opinion,  there  may  be  a  causal  relation  as  well  as  in  the  not  infrequent  occur- 
rence of  gall-stones  in  gouty  patients  (see  above)  with  or  without  simultaneous 
urolithiasis.  ( See  my  article,  "  Einige  Bemerkungen  über  die  Beziehungen 
zwischen  der  Gicht  und  den  Steinkrankheiten/'  Aerztliche  Praxis,  1901,  Nr. 
4,  where  I  have  discussed  these  questions  at  length.) 

I  shall  now  consider  the  condition  of  the  kidneys  in  primary  arthritic  gout. 

At  the  autopsy  of  those  who  have  suffered  from  this  disease,  the  kidneys 
may  be  found  quite  sound  and  normal,  even  in  the  cases  in  which  decided 
gouty  changes  in  the  joints  had  taken  place.  In  other  cases,  the  kidneys  are 
variously  altered  by  the  morbid  process.  "We  find  chronic  interstitial  changes 
with  especial  frequency,  usually  the  picture  of  genuine  contracted  kidney. 
With  this,  amyloid  degeneration  of  the  kidney  is  often  found.  Deposits  of 
urates  may  be  entirely  absent  in  the  kidney  and  in  such  cases  we  are  unable 
to  recognize  the  etiology  from  the  anatomical  changes.  In  other  cases  besides 
a  more  or  less  advanced  nephritis,  urate  crystals  are  found  in  the  uriniferous 
tubules.  Even  this  condition  I  do  not  believe  to  be  characteristic  of  gout. 
Finally,  we  may  note  in  the  degenerated  kidneys  typical  foci  of  necrosis  with 
urate  deposits  which  closely  resemble  gouty  tophi,  both  consisting  of  mono- 
sodium  urate  (Tollens).  Nephritis  due  to  gout,  in  the  main,  shows  the  same 
symptom-complex  as  when  due  to  other  etiologic  factors.  So-called  gouty 
gonorrhea  has  been  much  discussed;  it  is  certainly  a  rare  affection,  in  which, 
in  so  far  as  I  have  been  able  to  form  an  opinion,  we  are  principally  concerned 
with  a  catarrh  of  the  excretory  ducts  of  the  prostate. 

Inflammation  of  the  mucous  membranes  of  the  respiratory  organs  is  by 
no  means  rare  in  gout,  and  this  is  not  remarkable  in  view  of  what  has  been 
stated  regarding  gouty  disease  of  the  mucous  membranes.  No  further  expla- 
nation is  required  concerning  the  way  in  which  gout  produces  this  complica- 
tion, nor  why  in  this  disease  there  is  a  predisposition  to  nutritive  disturbance 
of  the  lungs  themselves,  which  favors  the  development  of  pulmonary  emphy- 
sema. It  is  also  evident  that  gout  by  no  means  excludes  the  development  of 
pulmonary  tuberculosis  and  other  affections  of  the  lungs.  Pulmonary  tuber- 
culosis and  gout  not  infrequently  occur  in  combination.  In  the  larynx  specific 
gouty  processes  also  occasionally  take  place. 

The  symptoms  on  the  part  of  the  nervous  system  are  of  special  interest. 
As  is  well  known,  many  celebrated  clinicians  have  maintained  the  opinion,  to 
which  some  still  adhere,  that  gout  is  essentially  a  trophoneurosis,  or  a  disturb- 
ance of  the  nutritive  function.  This  need  not  be  here  discussed.  Certainly 
disturbances  in  all  parts  of  the  nervous  system  often  accompany  gout,  but 
many  of  the  usual  cerebral  affections  are  due  to  vascular  changes  produced  in 
the  course  of  the  malady.  Diseases  of  the  cerebral  vessels  have  frequently 
been  proven  to  be  the  cause  of  severe  diseases  of  the  brain,  for  example,  of 
cerebral  hemorrhage. 

Often,  however,  in  primary  arthritic  gout,  so-called  general  neuroses  are 
observed,  i.  e.,  those  affections  of  the  central  nervous  system  for  which  no 
constant  material  substratum  can  be  found.  Among  these  I  must  first  men- 
tion the  severe  neurasthenic  conditions  which  sometimes  reach  the  highest 
degree   of  hypochondriac   depression,   and   which    in   some  cases   may   even 


SYMPTOMATOLOGY  143 

occur  in  paroxysms.  In  this  group  also  belongs  vertigo,  which,  however, 
as  experience  has  taught  me,  may  also  be  due  to  disease  of  the  audi- 
tory apparatus  in  connection  with  gout.  Here  we  must  also  mention  migraine 
bo  commonly  associated  with  gout,  but  which  apparently  develops  under  vary- 
ing condition-.  Gouty  paralyses  and  neuralgia*,  among  which  we  find  the 
visceral  form,  arc  in  many  cases  due  to  neuritis.  The  gouty  affections  of  the 
organs  of  special  sense, in  which, perhaps,  those  of  the  eye  fill  a  prominent  place, 
require  description  by  a  specialist.  It  need  only  here  be  remarked  that  glau- 
coma, so  far  as  I  am  able  to  understand  the  condition,  is  usually  due  to  gout. 

That  gout  plays  a  prominenl  role  in  the  etiology  of  cutaneous  affections 
cannot  Be  doubted.  We  have  already  described  the  gouty  inflammation  of  the 
skin  in  the  paroxysms;  to  these  also  helong  the  so-called  copper  nose  which  is 
not  always  due  to  gout,  but  arises  so  frequently  in  gouty  patients  that  a  causal 
relation  between  them  may  be  looked  upon  as  very  likely.  This  appearance  of 
"rhinagra,"  which  usually  run-  a  chronic  course  in  this  prominent  portion 
of  the  human  countenance,  must  be  considered  analogous  to  the  gouty  proces 
in  the  ear.  However,  within  the  limits  of  my  experience,  necrotic  proci 
of  the  skin  rarely  occur  in  the  nose,  and,  therefore,  gouty  tophi  are  absent 
there.  In  regard  to  gouty  concretions  in  the  skin  and  in  the  subcutaneous 
connective  tissue  of  the  various  regions  of  the  body,  it  is  unnecessary  to  speak 
further.  Occasionally  lymphangitis  is  seen  as  a  consequence  of  gout.  This 
condition  does  not  give  rise  to  difficulties  according  to  the  views  which  I  have 
formeil  of  the  pathogenesis  of  primary  arthritic  gout.  Gouty  eczema  and 
gouty  psoriasis  are  frequently  mentioned.  It  is  at  once  evident  thai  in  the 
development  of  the  former  the  irritation  of  the  skin  in  gout.  Like  the  gouty 
inflammation  of  the  mucous  membranes,  forms  a  predisposing  factor.  In 
psoriasis,  of  the  cause  of  which  we  know  so  little,  I  have  not  succeeded  in 
deducing  any  reliable  connection  between  it  and  gout;  I  do  not,  however,  by 
any  mean-  desire  to  deny  the  existence  of  such  a  connection,  particularly  as 
psoriasis  and  goul  so  often  occur  side  by  side.  The  same  is  also  tn f  cer- 
tain cutaneous  affections  which  may  be  referred  to  vasomotor  disturbance, 
among  which  T  desire  primarily  to  call  attention  to  urticaria,  which  often 
appears  as  a  chronic  affection  in  gouty  women.  That  these  cutaneous  affec- 
tions are  invariably  due  to  gout  I  naturally  do  not  believe.  Finally,  it  may 
here  be  mentioned  that  alopecia  is  sometimes  found  associated  with  gout, 
although  in  these  cases  quite  a  number  of  other  etiologic  factor-  may  bring 
about  the  condition. 

At  this  place  only  a  review  of  the  more  frequent  symptoms  in  so-called  vis- 
ceral gout  can  be  given.  In  the  consideration  of  the  diseases  which  occasion- 
ally accompany  gout,  the  question  will  and  must  occur  whether  there  is  actually 

a  causal  connection  between  them.     If  we  reflect  that  in  gout  all  tl rgans 

arc  subject  to  a  certain  tissue  irritation,  we  shall  be  inclined  to  regard  many 
diseases  as  due  to  gout.  The  fact  is  of  interest  that  celebrated  French  inves- 
tigators, such  as  l'.a/in  and  Ch.  Bouchard,  are  of  the  opinion  that  cam 
the  result  of  pout.  The  former  has  even  said  that  gouty  patients  are  par- 
ticularly apt  to  succumb  to  cancel-,  especially  to  cancer  of  the  rectum  or  of 
the  bladder.     I   shall  not  enter  into  this  in  detail.     On  the  other  hand,  the 


144  GOUT 

fact  must  be  expressly  pointed  out  that  gout,  obesity  and  diabetes  mellitus 
are  intimately  related,  which  is  evident  from  the  circumstance  that  two  of 
these  diseases,  or  not  infrequently  all  three,  simultaneously  occur  in  the  same 
person.  There  is  an  extensive  literature  regarding  the  connection  between 
obesity  and  gout.  Some  look  upon  obesity  and  gout  as  inseparable  accom- 
paniments of  one  another.  Still  I  must  emphatically  state  here  that  gouty 
patients  are  by  no  means  all  fat.  Many  are  so,  but  even  these  may  emaciate 
after  they  have  become  cachectic  as  the  result  of  gout.  Certainly  there  are, 
as  has  been  stated,  many  fat  gouty  patients,  and  I  may  here  refer  to  my  arti- 
cle upon  obesity,  in  which  I  mentioned  such  a  case  occurring  in  my  practice, 
and  took  occasion  to  discuss  the  relation  between  gout  and  obesity  somewhat 
more  in  detail.  This  observation  is  specially  interesting  because  it  concerns  a 
lady  who  had  well  developed  typical  attacks  of  gout,  which  are  by  no  means  so 
rare  as  is  usually  supposed,  but,  on  the  contrary,  in  my  experience,  are  fre- 
quent enough  in  women  suffering  from  obesity.  In  discussing  obesity,  I  re- 
ferred to  the  development  of  fat-foot  which  we  occasionally  observe  with  in- 
creasing corpulence,  particularly  in  persons  with  a  hereditary  predisposition  to 
obesity  and  gout;  these  are  mostly  young  individuals  of  either  sex.  The  rela- 
tions between  gout  and  diabetes  mellitus  need  not  be  here  considered.  But  it 
may  be  noted  that  gouty  and  diabetic  symptoms  not  infrequently  alternate  with 
one  another,  a  fact  which  causes  the  diabetes  to  assume  a  somewhat  intermittent 
character.  Tbe  excretion  of  sugar  is  then  slight,  as  a  rule,  and  the  so-called 
diabetes  arthriticus  frequently  shows  a  course  similar  to  that  described  by 
Johann  Peter  Frank  as  diabetes  decipiens.  A.  Gilbert  and  Emil  Weil  attrib- 
ute this  form  of  diabetes  mellitus  to  an  insufficient  or  entirely  absent  function 
of  the  liver.  Alimentary  and  rapidly  disappearing,  so-called  simple,  glyco- 
surias, which  I  always  look  upon  with  suspicion,  are  not  so  rare  in  gout. 

We  must  now  consider  the  relation  between  gout  and  rheumatism.  What 
is  to  be  understood  by  this?  First,  there  are  a  number  of  so-called  cases  of 
chronic  arthritic  rheumatism  which  should  be  considered  as  gout.  When  per- 
sons about  fifty  years  of  age,  who  have  previously  never  suffered  from  any 
disease  resembling  acute  articular  rheumatism,  are  attacked  by  an  afebrile 
disease  which  particularly  implicates  or  almost  exclusively  affects  the  small 
joints,  which  is  accompanied  by  inflammatory  symptoms,  and  which  runs  its 
course  with  acute  exacerbations,  gout  should  first  be  thought  of.  This  is  also 
true  of  the  cases  in  which  the  joints  show  a  certain  deformity,  and  in  which 
we  usually  recognize  the  presence  of  so-called  deforming  articular  rheumatism, 
a  disease  which  probably  has  no  uniform  etiology.  An  investigation  of  the 
family  history  certainly  plays  an  important  role  in  the  diagnosis  of  such  cases. 
Further,  in  considering  the  relation  of  rheumatism  to  gout  it  must  be  remem- 
bered that  rheumatism,  like  all  morbid  processes  that  damage  the  joints,  when 
combined  with  the  gouty  predisposition,  furthers  the  development  of  gout, 
for  anything  that  limits  the  free  circulation  of  the  fluids  in  the  extremities 
favors  the  development  of  gout  in  persons  who  are  predisposed. 

Rheumatism  not  only  attacks  the  joints  but  all  their  component  parts,  i.  e., 
the  muscles  as  well,  and  must  be  looked  upon  as  a  more  or  less  active  occa- 
sional cause  of  gout.    In  a  similar  manner  connecting  links  of  relationship  may 


COURSE  AXD  PROGNOSIS  1  15 

be  found  between  front  and  a  number  of  other  pathologic  processes.  From 
sucb  point-  of  view  we  may  explain  the  well-known  relations  of  syphilü 
gout,  which  diseases  frequently  occur  simultaneously.  I  believe  that  tbe 
explanation  of  this  association  may  be  that  syphilis  in  a  person  predisposed  to 
gout  frequently  precipitates  an  outbreak.  Tt  is  a  fact  that  in  the  beginning 
of  the  secondary  stage  in  syphilitics  the  limbs,  and  particularly  the  joints, 
small  and  large,  are  especially  implicated.  Any  one  who  fails  sufficiently  to 
consider  this  in  treatment  misses  a  very  important  curative  guide.  Tt  is  cer- 
tainly difficult,  from  the  nature  of  the  changes  in  the  joints,  and  when  gouty 
tophi  are  not  present,  to  say  that  this  i-  ä  case  of  true  gout  and  that  is  one 
of  rheumatism.  These  difficulties  at  once  disappear  if  we  consider  the  history 
of  the  so-called  Heberden's  nodes.  By  this  term  we  understand  the  thicken- 
ing of  the  joints  of  the  middle  and  end  phalanges  of  the  three-jointed  fingers. 
Some  authorities  consider  these  joint  deformities  aa  gouty;  other-  look  upon 
them  as  of  rheumatic  origin.  In  my  experience  such  processes  certainly  may 
arise  from  a  gouty  basis;  upon  the  other  hand,  we  can  by  no  means  always 
prove  that  gout  is  the  cause  of  these  joint  thickenings.  We  are  not  justi- 
fied in  concluding  from  the  same  external  manifestation  of  a  path"!  _ 
change  a  similarity  in  the  cause  of  the  disease.  A  case  in  point  is  the  con- 
tracture of  the  aponeurosis  palmaris  which  has  1 n  named,  after  the  cele- 
brated surgeon  Dupuytren,  Dupuytren's  contracture.  It  was  incorrectly  main- 
tained that  this  by  no  mean-  rare  affection  was  always  due  to  gout.  This 
may  be  the  case:  it  is  not,  however,  necessarily  so.  At  all  events  such  obscure 
combinations  in  practice  are  not  to  be  underestimated,  since  diversity  of  symp- 
toms always  awaken-  interest,  and  for  the  affected  patient,  that  is,  for  his  etio- 
logic  treatment,  the  elucidation  of  such  questions  is  of  the  greatesl  importance. 

COURSE   AND    PROGNOSIS 

The  course  of  gout,  as  shown  by  the  previous  description,  is  subjed  to 
many  variations,  the  majority  of  which  may  be  understood  by  supposing  that 
in  individual  cases  there  is  a  varying  intensity  in  the  predisposition  to  the 
disease,  as  well  as  in  the  influence  exerted  by  manifold  occasional  causes  in 
producing  the  condition.  Goui  is  a  disease  of  extremely  chronic  course.  The 
earlier  the  vital  organs,  such  a-  the  heart,  the  vascular  Bystem,  and  the  kid- 
ney-, are  implicated  the  sooner  does  a  fatal  resull  ensue.  So  long  as  goui 
remain.-  Limited  to  the  extremities,  it  i-  a  comparatively  harmless  although 
very  irksome  disease.  A-  n  i-  often  caused  by  the  fault  of  the  patient,  it 
frequently  make-  him  the  -port  of  his  associates  and  so  irritate-  him.  For 
tin-  reason,  the  gouty  patient  with  his  "Weh  und  Ach  so  tausendfach"  and 
his  "  Zippern  "  i-  rarely  the  recipient  of  sympathy.  People  forge!  entirely 
that  even  an  apparently  mild  attack  of  goui  may  be  very  serious,  either  be- 
cause it  may  throw  itself  upon  the  "  internal  part-.*"  as  the  laity  Bay,  or. 
to  use  a  more  scientific  expression,  when  it  becomes  retrocedent,  because  com- 
plication- ensue  or  because  the  patient-  become  cachectic.  Nevertheless  a 
gouty  patient,  in  spite  of  periodically  recurring  attack-  of  moderate  intensity, 
may  reach  very  old  age  provided  no  intercurrent  affections  arise. 
it 


146  GOUT 


DIAGNOSIS 


The  diagnosis  of  primary  gout  depends  upon  the  presence  of  two  symp- 
toms, namely,  the  typical  attack  and  the  gouty  tophi.  Either  of  these,  pro- 
vided that  it  has  been  determined  with  absolute  certainty,  may  in  itself  be 
looked  upon  as  proof  positive.  It  is  not  necessary  to  repeat  here  by  what 
means  we  may  determine  beyond  doubt  the  presence  of  these  two  symptoms. 
I  have  endeavored  in  the  description  of  the  symptomatology  to  mention  these 
factors  briefly,  but  to  characterize  them  definitely.  Neither  the  joint  phe- 
nomena, nor  skiagraphy  of  the  affected  joints,  are  by  any  means  such  positive 
proof  as  to  deserve- the  confidence  of  the  physician  in  the  diagnosis  of  primary 
arthritic  gout.  The  same  is  true  of  the  uric  acid  contents  of  the  blood,  of 
the  serum  from  blisters,  which  is  used  in  Garrod's  so-called  thread  test,  as 
well  as  of  the  uric  acid  contents  of  the  urine.  Such  findings  are  by  no  means 
to  be  undervalued;  but  the  data  gained  in  this  way  cannot  as  yet  well  be 
utilized  in  practice.  They  do  not  increase  our  diagnostic  certainty.  On  the 
other  hand  the  recognition  of  a  family  predisposition,  as  well  as  the  history 
of  the  patient  in  other  respects,  is  of  inestimable  value. 

There  are  certain  symptoms  the  consideration  of  which  is  important,  par- 
ticularly those  which  we  have  learned  to  recognize  as  premonitory  or  inter- 
mediate. These,  too,  are  by  no  means  positive,  yet  they  often  as  pathfinders 
lead  us  to  success.  This  is  true,  for  example,  of  lumbago,  especially  if  it 
occurs  frequently  without  other  determinable  etiologic  factor,  and  is  quite 
persistent.  It  is  likewise  true  of  the  frequently  recurring  severe  cramps  in 
the  calves,  and  of  neurasthenia.  I  have  always  laid  stress  upon  the  fact  that 
a  great  number  of  neurasthenics  owe  their  neurasthenia  to  a  gouty  predispo- 
sition which  acts  by  limiting  their  energy.  Special  difficulty  in  diagnosis  is 
often  met  with  in  women,  when  no  typical  well-developed  attacks  of  gout 
occur.  Here  the  characteristic  gouty  tophi  are  sometimes  absent,  but,  on  the 
other  hand,  we  may  find  the  Heberden  nodes.  I  have  previously  mentioned 
that  in  women  true  typical  gouty  paroxysms  occasionally  occur  even  although 
they  do  not  have  the  same  acuteness  and  intensity  as  the  gouty  attacks  of 
men.  In  such  cases  the  investigation  of  the  etiology  is  important.  It  must 
also  be  maintained  that  not  infrequently  gouty  paroxysms  can  be  recognized 
as  consequences  of  trauma.  To  the  category  of  these  belong  a  number  of  joint 
affections  which  are  called  "  sprain  of  the  ankle,"  "  stretching  of  the  tendons," 
etc.  Such  errors  are  especially  prone  to  happen  in  dealing  with  children  as 
gout  is  usually  not  looked  for  in  them.  These  mistakes  may  be  explained  by 
the  fact  that,  as  a  rule,  a  slight  trauma  precedes  the  gouty  attacks,  and  this  is 
just  as  predisposing  for  the  onset  of  the  gouty  attacks  as  the  other  etiologic 
factors  that  have  been  enumerated. 

TREATMENT 

For  all  practical  purposes  the  treatment  of  primnrj/  arthritic  govt  may  be 
divided  into  two  parts.  First,  we  will  consider  the  treatment  of  gout  as  a 
whole,  including  the  treatment  of  the  gouty  predisposition,  and  secondly,  the 


TREATMENT  147 

treatment  of  the  so-called  acute  gout,  the  typical  gouty  attack  or  the  gouty 
paroxysm.  In  the  treatment  of  the  gouty  process  as  a  whole,  prophylaxis  plays 
a  most  important  part.  The  latter  appears  simple  enough,  provided  we  are 
correct  in  assuming  that  gout  depends  for  its  development  and  existence  upon 
a  manner  of  life  which  deviates  from  the  normal.  Seneca,  the  celebrated  Stoic 
philosopher,  who  lived  in  the  first  century.  a.D..  lamented  that,  in  his  age, 
the  women  who  were  living  in  the  same  opulent  manner  as  the  men  showed 
the  same  tendency  to  gout  as  the  men,  while  in  the  age  of  Eippocrates  women 
were  almost  exempt  from  gout.  In  general  this  is  true,  for  Hippocrates  says 
expressly  that  women  do  not  suffer  from  gout  except  when  their  menses  cease. 
There  is,  therefore,  some  truth  in  the  words  of  Seneca,  and  since  that  time 
moderation  has  been  continuously  taught.  I  will  quote  the  advice  of  Thomas 
Sydenham  in  regard  to  the  treatment  of  gout.  He  says  (Medical  Works, 
Translated  by  J.  J.  Marstaler,  Vienna,  1787,  ii.  p.  312)  :  "In  the  first  place, 
then,  moderation  must  he  observed  in  meat  and  drink,  so  thai  the  stomach 
will  receive  no  more  food  than  it  can  digest,  and  no  fresh  fuel  be  added  to  the 
disease.  The  other  extreme,  however,  as  I  have  found  in  my  own  person,  is 
equally  injurious.  Abstinence  weakens  the  parts  by  withholding  their  due 
proportion  of  that  aliment  which  is  necessary  for  supporting  their  strength 
and  vigor." 

In  regard  to  the  diet  of  gouty  patients  and  of  those  persons  who  have  a 
family  predisposition  to  gout,  the  same  rules  are  to  he  observed  as  in  the  nutri- 
tion of  the  obese.  The  view  formerly  maintained  that  the  use  of  fat  increases 
the  formation  of  uric  acid  has  been  shown  to  be  entirely  erroneous  by  investi- 
gations carried  out  in  regard  to  the  ingestion  of  fat.  The  amount  id'  albumin 
permitted  to  gouty  patient.-  must  not  he  deficient.  Everything  that  weakens 
the  body  and  diminishes  the  activity  of  the  gouty  patient  influences  the  gouty 
process  unfavorably.  On  the  other  hand,  the  administration  of  large  quanti- 
ties of  meat,  as  experience  has  shown,  is  decidedly  deleterious  to  the  gouty.  1 
believe  it.  therefore,  in  the  nutrition  of  gouty  patients,  to  be  not  only  advisable 

hut  eveu   necessary  to  employ  vegetable  albumin    in   the  manner  mentioned   by 

me  in  the  treatment  of  obesity.  I  am  even  willing  to  maintain  that  for  gouty 
patient-  a  vegetarian  diet  with  the  necessary  amount  of  vegetable  albumin 
forms  the  mosl  suitable  plan  of  nutrition.  Milk  and  milk  products  may  fur- 
nish the  variety  which  is  grateful  to  the  patient.  Eggs  also,  if  taken  in  mod- 
eration, may  be  permitted.  White  meat  is  looked  upon  as  better  than  dark. 
Alcohol,  no  matter  what  its  form,  LS  poison  for  the  gouty  patient  and  for  all 
those  who  are  predisposed  to  the  affection.  Only  when  the  physician  for  defi- 
nite reasons  declares  it  to  be  necessary,  is  the  amount  prescribed  by  him  to 
be  employed.  The  most  suitable  drink  for  gouty  patients  is  ordinary  good 
drinking-water  or  mild  alkaline  waters.  I  frequently  order  that  from  the 
Offenbach  Kaiser  Friedrich  Spring,  which  in  my  opinion  is  preferable  to  all 
other  alkaline  mineral  water-  on  account  of  its  alight  amount  of  alkali.  For 
this  reason,  drugs  containing  vegetable  acids  thai  are  excreted  in  the  urine 
in  the  form  of  carbonates  should  be  nsed  in  the  treatment  of  gout.  The 
cherry  cure  and  the  strawberry  cure  are  nol  improperly  named.  These  fruits 
contain  alkalies  rich  in  vegetable  acid.     On  the  other  hand,  much  harm  la 


148  GOUT 

done  by  the  so-called  lemon  cure.  Patients  eat  so  much  of  this  fruit  that 
frequently  troublesome  dyspeptic  symptoms  arise.  Neither  do  the  grape  cures 
bring  about  what  was  formerly  expected  of  them.  Sometimes  they  are  fol- 
lowed by  annoying  gastric  symptoms  and  even  serious  digestive  disturbances. 
Moderation  in  eating  and  drinking  is  the  first  duty  of  the  patient,  but,  not- 
withstanding this,  the  avoidance  of  all  antifat  cures,  i.  e.,  all  measures  liable 
to  produce  inanition,  should  be  a  guiding  principle.  In  this  connection  the 
immoderate  use  of  alkalies  which  are  so  frequently  advised,  chiefly  on  account 
of  their  uric  acid  solvent  properties,  is  injudicious. 

Mineral  spring  cures  and  bath  cures  are  frequently  resorted  to  in  gout,  and 
the  Hi  ermal  baths  enjoy  a  great  reputation.  I  usually  advise  them  for  patients 
who  cannot  take  necessary  muscular  exercise  such  as  gymnastics,  mountain 
tours,  etc.  The  same  is  true  of  baths  as  of  the  employment  of  mineral  water 
and  bath  cures  in  obesity,  which,  as  we  have  seen,  often  accompanies  gout. 
The  thermal  baths  are,  in  general,  to  be  reserved  for  (a)  such  cases  of  gout  as 
occur  in  decrepit  persons,  (&)  for  old  persons  for  whom  energetic  muscular 
activity  is  no  longer  possible,  (c)  for  cases  of  gout  in  which  exudates  have 
formed  in  the  joints  and  in  which  resorption  is  to  be  brought  about,  and  (d) 
for  cases  in  which  complications  make  such  a  treatment  necessary.  From  this 
point  of  view  peat  baths  and  mud  baths  are  in  many  cases  very  serviceable. 
The  sulphur  mud  baths  in  Pistyan  in  Upper  Hungary  as  well  as  the  mud  baths 
in  Germany  are  highly  recommended.  In  many  such  cases  of  gout  it  is  noted 
that,  when  all  other  remedies  fail,  sweat  baths  in  the  Grotto  of  Monsum- 
mano  or  in  the  Grotto  of  Bormio  give  very  excellent  results.  Carlsbad,  Wies- 
baden, Aix-la-Chapelle,  Vichy,  Wildbad  and  many  other  resorts  are  visited 
by  gouty  patients,  but  often  without  success  unless  they  are  assisted  by  suitable 
dietetic  measures.  It  is  of  greater  importance  successfully  to  combat  the 
morbid  processes  which  in  persons  predisposed  to  gout  form  active  auxiliary 
causes  in  its  development,  and  decidedly  favor  its  advance.  Among  these  may 
be  mentioned  rheumatic  affections  and  especially  syphilis.  In  beginning  a 
treatment  of  gout,  it  should  always  be  determined  whether  syphilis  has  pre- 
ceded it  or  not. 

There  are  quite  a  number  of  so-called  specific  remedies  for  gout.  Those 
which  diminish  uric  acid  formation,  that  is,  which  render  the  urates  more 
soluble,  play  an  important  role.  Of  these  remedies  lithium  has  been  for  a 
long  time  in  the  van.  It  can  only  be  administered  as  lithium  carbonate,  not 
as  lithium  chlorid.  I  have  been  unable  to  convince  myself  of  the  value  of 
this  remedy.  Urotropin,  introduced  into  practice  by  A.  Nicolaier  (twice  daily 
a  dose  of  0.5  gram,  7^  grains,  each  tablet  dissolved  in  a  quarter  of  a  liter  of  a 
slightly  alkaline  water),  is  better.  But  further  investigations  concerning  its 
use  are  necessary.  I  have  heard  it  praised  by  a  number  of  old  gouty  patients 
who  had  tried  almost  everything.  Piperazin  (about  1  to  2  grams  daily  in  an 
alkaline  water)  has  proven  useful,  particularly  for  the  "rheumatic"  pains  in 
chronic  arthritic  gout.  The  importance  of  treating  the  very  defective  intes- 
tinal function  in  the  course  of  gout  (constipation)  is  not  to  be  underestimated. 
This  disturbance  of  intestinal  digestion  must  be  relieved,  and,  as  a  rule,  I 
employ  large  enemata  of  oil.     That  plentiful  exercise  is  beneficial  and  neces- 


TREATMENT  149 

sary  to  the  gouty  patient,  requires  no  further  explanation.  As  long  as  his 
strength  permits  this  must  he  kept  up.  I  have  already  stated  that  in  these 
cases  I  prefer  muscular  exercise  to  all  other  methods.  I  f  the  gouty  paroxysms 
do  not  occur  so  suddenly  and  are  not  bo  severe  that  the  patit-nt  must  go  to  bed, 
he  should  remain  as  long  as  possible  upon  his  feet.  When,  however,  the 
patient  cannot  walk,  and  the  affected  member  cannot  be  moved,  "  patience  and 
cotton"  as  many  old  gouty  persons  say,  are  the  besl  remedies;  other-  pr 
the  Laville  liqueur,  which  is  probably  beneficial  on  account  of  the  Colchicum 
which  it  contains.  Colchicum  is  also  administered  as  a  tincture,  or  in  combina- 
tion with  opium,  purgatives,  and  potassium  iodid.  Pure  crystalline  colchicin 
has  lately  been  recommended  in  doses  of  one  milligram.  Such  powerful  reme- 
dies should  naturally  only  be  taken  under  the  advice  and  supervision  of  the 
physician.  But  only  too  frequently  persons  subject  to  gouty  attacks  refuse 
professional  aid  and  attempt  to  cure  themselves.  The  so-called  antirheumat- 
ics, e.g.,  the  salicylates,  are  also  valuable  occasionally  for  the  relief  of  pain, 
although  in  the  present  status  of  our  knowledge,  they  cannot  be  advised  as  a 
rat  ional  remedy  for  gout. 

The  various  symptoms  and  complications  of  gout  should  be  treated  accord- 
big  to  special  indications.  Here  we  will  only  consider  the  treatment  of  the 
numerous  aervous  symptoms,  especially  the  therapy  of  gouty  neuralgia  with 
its  related  conditions,  and  the  functional  cardiac  disturbances  which  so  fre- 
quently occur  in  the  gouty.  Where  there  is  chronic  constipation,  the  treat- 
ment previously  mentioned  for  the  evacuation  of  the  intestine  filled  with 
feces  i-  of  paramount  importance.  Even  if  chronic  constipation  is  not  presenl 
a  useful  auxiliary  remedy  in  intestinal  treatment  is  the  employment  of  arsenic 
and  iron,  preferably  in  the  form  of  iron  water-  containing  arsenic.  In  general 
it  is  advisable  to  begin  with  the  mildest  water  of  the  Levico-Vetriolo  in  the 
Valsugana  (South  Tyrol).  A  residence  in  tin-  region,  which  i-  easily  acces- 
sible, is  to  be  preferred  to  the  ose  of  the  arsenic-containing  mineral  water  at 
home,  for  the  place  i-  luxuriously  furnished  with  all  curative  agents  that  arc 
effective  in  gout,  and  i-  al-o  advisable  on  account  of  its  climate.  There  are 
many  cases  of  so-called  "  larva]  "  gout,  which  cannot  readily  be  diagnosticated, 
yet  are  particularly  benefited  by  such  cures.  Cure-  of  this  kind  are  al-o  very 
suitable,  mutatis  mutandis,  for  such  gouty  patients  a-  are  already  decrepit 

and    have   reached    the  BO-called   cachectic    stage  of  gout.      The   many  curative 

agents  which  nature  and  science  there  furnish,  may  he  adapted  in  various  ways 
by  expert  physicians  to  the  individual  needs  of  the  patients,  in  these  decrepit 
gouty  patient-  no  kind  of  -o-called  -pecific  treatment  i-  to  he  used,  and  Col- 
chicum especially  is  badly  borne.  Only  tonic  treatment — adjusted  to  the  con- 
dition— is  advisable.  In  the  surgical  treatment  of  gouty  tophi,  all  the  precau- 
tion- of  antiseptic  surgery  are  of  course  to  he  observed. 

A  few  words  mu-t  he  devoted  b>  the  consideration  of  primary  renal  gout, 
by  which  we  mean  the  most  serious  form  of  gout,  in  which  a  generalized   uric 

acid  engorgemenl  arises  a-  the  resull  of  a  severe  renal  affection  and  usually 
consists  in  a  chronic  and.  particularly,  in  an  interstitial  inflammation  of  the 
kidneys.  In  (his  renal  inflammation,  the  gout  it-elf  i-  an  important  patho- 
genetic factor.     At  all  event-,  in  primary  renal  gout   the  renal  -ymptom- 


150 


GOUT 


the  earliest  ones,  and  the  joint  symptoms  are  secondary.  When  the  latter  de- 
velop, the  nephritic  process  is  usually  so  far  advanced  that  the  gouty  nature 
of  the  affection  can  only  be  determined  at  autopsy,  partly  from  the  gouty 
changes  in  the  kidney,  partly  from  the  gouty  changes  in  the  individual  joints, 
particularly  the  first  metatarsophalangeal  joint.  Fortunately  this  form  of 
gout  is  not  very  frequent.  The  diagnosis  during  life  is  only  possible  when  the 
conditions  just  described  are  recognized  in  the  affected  person.  If  the  diag- 
nosis of  primary  renal  gout  has  been  made,  the  prognosis  is  grave,  as  in  all 
severe  interstitial  renal  inflammations,  since  the  renal  parenchyma  is  destroyed. 
The  therapy  should  be  directed  to  the  renal  affection,  for  which  diaphoresis 
and  the  dietetic  treatment  mentioned  in  primary  arthritic  gout  are  first  to 
be  tried. 


OBESITY 
By  W.   EBSTEIN,  Göttingen 

We  understand  by  obesity  an  excessive  infiltration  of  fat  into  the  con- 
nective tissue  in  areas  of  the  body  whore,  also  in  healthy  individuals,  fat  is 
found  in  varying  quantities.  The  chief  points  of  deposit  of  fat  arc  the  sub- 
cutaneous connective  tissue  and  the  mesentery.  Special  parts  of  the  subcu- 
taneous connective  tissue  are  particularly  involved,  chiefly  the  abdomen.  In 
the  region  of  the  breasts  the  deposit  of  fat  may  also  reach  enormous  grades. 
The  female  breasl  has  been  known  to  attain  a  weight  of  33  pounds.  The  high- 
est grades  of  corpulence  we  designate  obesity.  In  this  condition  fat  also  col- 
lects' in  regions  where  under  normal  conditions  fat  can  hardly  he  perceived. 
Larrey,  who  accompanied  Napoleon  I  as  chief  surgeon  in  all  of  hi-  campaigns, 
-aw  in  the  Arabs  in  Syria  scrota  which  attained,  owing  to  fat  formation,  the 
size  of  a  bulging  cow's  udder  though  under  the  skin  of  the  normal  scrotum 
only  a  very  scanty  loose  connective  tissue  is  found.  Fat  may.  therefore,  appear 
even  in  this  region  and  in  great  quantity.  In  regard  to  the  words  in  common 
use  to  designate  obesity  something  may  he  added  in  the  way  of  definition. 
Adipositas  is  a  term  often  used  and  this  designation  is  quite  clear.     A  more 

era!  term  is  obesity;1  the  French  speak  of  obesite.  The  word  is  derived 
from  "oh"  and  "  edere/'  and  means  literally  "to  eat  up  quickly."  In  Eng- 
lish the  term  corpulence  is  generally  employed — a  term  which  i<  also  used 
by  the  (Jcrmans,  hut  not  to  indicate  the  most  marked  grades  of  obesity.  Tn 
the  excellent  hook  of  William  Osier:  The  Principle-  and  Practice  of  Medi- 
cine, third  edition  (  Ww  York  and  London).  1898,  page  139,  the  disease  is 
described  under  the  name  of  obesity,  and  it  is  mentioned  that  Lord  Byron 
who  was  hini-e|f  quite  fat.  a-  i-  well  known,  defined  the  condition — "  oily 
dropsy."  The  designations  "pimelosis"  and  "physconia"  are  hut  little  em- 
ployed. Like  the  other  terms  just  discussed,  pimelosia  refers  directly  to  the 
main  factor  of  the  disease,  being  derived   from  the  Greek  word   "jnpekq" 

'  According  to  the  Latin  dictionary  of  Forcellinus,  tli«'  word  "obeaitaa"  occurs  in 
tin-  writings  of  Columella  (a  contemporary  of  Celsus  and  Seneca),  aboul  the  middle 
of  tin'  lir-t  century  a.D.,  and  in  Suetonius  (according  t<>  Teuffel's  History  >>\  Etonian 
Literature,  aboul  n">  a.D.  to  L60  \.i>.  i .  The  former,  in  hi-  "de  re  rustic«  "  n.  24,  writes: 
••  \c  Bteriles  eaa  reddat,  nimia  corporis  obesitas."  The  latter  mentions  in  Hi-  biography 
of  Domitian  (18),  thai  lie  \\;i-  disfigured  by  a  bald  head  as  well  as  by  "obesitate 
ventris."  Further,  Suetonius  in  hi-  history  of  the  life  of  Claudius  (41)  tells  us  that 
laughter  was  provoked  "defractis  compluribus  »ubselliis  obesitate  cujuadam."  In  the 
Historie  Naturalis,  Pliny  the  ':/</«»■  (born  -■'>  a. im  mentions  il7.-J7i  thai  certain  I 
also  "  laboranl  obesitate." 

151 


152  OBESITY 

(=  fat) .  Hyrtl  (Text-Book  of  Human  Anatomy,  20th  edition,  Vienna,  1889, 
p.  114)  holds  that  the  word  constructed  by  pathologists,  "  pimelosis,"  is  quite 
superfluous,  since  the  Greek  physicians  already  had  a  word  for  this  disease, 
namely  71-10-7-775.  Physconia,  from  "6  ^u'o-Ktov,"  big-bellied,  is  the  nickname 
of  Ptolemy  the  Eighth,  Energetes  the  Second  (170  b.c.),  the  classic  prede- 
cessor of  Banting.  Occasionally  polysarcia  adiposa  (r/o-dpi,  flesh)  is  used  as 
a  synonym  for  obesity.  Strictly  speaking,  polysarcia  should  only  be  used  for 
that  stage  of  obesity  in  which  the  fat  patient  still  retains  his  muscular  power, 
as  is  occasionally  observed  at  the  beginning  of  the  disease.  But  frequently 
such  persons  suffer  from  muscular  weakness  at  the  very  onset  of  obesity. 
Among  many  other  designations  for  obesity,  lipomatosis  universalis  may  be 
mentioned — a  term  which  is  used  as  a  synonym  for  the  highest  grades  of 
obesity.  The  fat  which  is  normally  present  about  the  epicardium  attains 
decided  development,  and,  for  example,  in  lipomatosis  cordis,  or  true  fatty 
heart,  we  note  that  the  myocardium  almost  completely  disappears  before  the 
proliferating  fat  which  permeates  it. 

That  fat  people  have  existed  since  the  coming  of  man  is  in  itself  probable, 
but  this  is  also  proven  by  the  oldest  records.  In  the  Book  of  Judges,  3,  21, 
we  read  that  Ehud  (a  left-handed  man  whom  Jahve  had  raised  up  to  deliver 
the  Israelites  from  the  bondage  of  Eglon  king  of  Moab),  in  obedience  to  God's 
command  put  forth  his  left  hand,  and  took  the  dagger  from  his  right  thigh, 
and  thrust  it  into  Eglon's  belly,  and  the  haft  also  went  in  after  the  blade,  and 
the  fat  closed  upon  the  blade,  so  that  he  could  not  draw  the  dagger  out  of  his 
belly;  for  Eglon  was  a  very  fat  man.  In  Psalms  73,  7,  there  is  written, 
"Their  eyes  stand  out  with  fatness:  they  have  more  than  heart  could  wish/' 
and,  finally,  in  the  Book  of  Job,  15,  27,  we  read:  "Because  he  covereth  his 
face  with  his  fatness,  and  maketh  collops  of  fat  on  his  flanks."  1  Whether 
obesity  was  a  matter  for  professional  treatment  among  the  Israelites  cannot 
be  determined  from  Biblical  records;  we  shall  revert  to  this  later.  In  the 
Hippocratic  writings  we  find  the  earliest  rules  regarding  the  treatment  of 
obesity — rules  which  hold  good  even  to-day.  In  the  art  of  the  Greek  mythol- 
ogy, Silenns  is  usually  represented  as  a  bald-headed  old  man  with  a  pug  nose, 
small  pig  ears,  and  pot-bellied,  a  typical  representation  of  obesity  in  the  stage 
which  I  have  designated  as  the  "ludicrous."  Kubens,  in  one  of  his  pictures 
has  graphically  portrayed  the  plump,  drunken  Silenus,  supported  by  a  negro 
who  walks  behind  him.  That  obesity  during  the  time  of  the  Roman  Emperors 
excited  ridicule  is  proven  by  the  previously  mentioned  quotation  from  Sue- 
tonius, and  Columella  alludes  delicately  to  the  prohibitive  influence  of  obesity 
upon  feminine  fertility.  Pliny  the  Elder,  who  was  almost  contemporaneous 
with  Columella,  formulated  rules  for  the  treatment  of  obesity  which  later  were 
generally  accepted.  These  ancient  views  have  lately  been  brought  forth  by 
some  authors  as  the  result  of  their  individual  investigations.  I  shall  subse- 
quently revert  to  this  again. 

Obesity  is  a  very  common  disease.  Indeed  L.  Traube  considers  that  a 
certain  amount  of  stoutness   (which  the  French  and  sometimes  the  Germans 

1  W.  Ebstein,  "  Die  Medicin  im  Alten  Testament,"  Stuttgart,  1900,  pp.  10  and  150. 


ETIOLOGY  153 

refer  to  as  "embonpoint"}  is  normal.  Healthy,  strong  children  are  usually 
plump  when  they  are  born.  This  fat  which  the  child  brings  into  the  world 
normally  increases  during  its  early  life,  but  later  it  decreases.  We  see  from 
this  that  a  certain  amount  of  adipose  tissue  is  to  he  looked  upon  as  normal  in 
the  child  at  birth  and  for  the  first  few  years  after  birth;  indeed  not  only  is 
it  normal  but  its  absence  indicates  something  abnormal.  An  excessive  amount 
of  body  fat.  however,  is  morbid  and  an  evil.  What  produces  such  an  excessive 
formation  of  body  fat? 

ETIOLOGY 

The  CAUSES  Ol  OBESITY  ean  be  best  understood  if  we  consider  for  a  moment 
the  process  of  fattening  animals,  which  forms  an  important  chapter  in  the 
science  of  farming.  The  stock  raiser,  whenever  he  is  raising  animals  for 
slaughter,  endeavors  to  increase  fat  as  well  as  to  produce  meat.  Many  experi- 
ences with  animals  have  shown  that  fodder  deficient  in  fat  as  well  as  that 
rieh  in  fat  will,  under  some  circumstances,  produce  a  profuse  accumulation  of 
fat.  Naturally,  this  presupposes  that  the  food  introduced  exceeds  the  amount 
required  to  maintain  the  animal,  and  that  albumin  products  are  also  present 
in  the  food  in  plentiful  amounts.  It  is  true  that  animals  can  he  fattened 
with  fat  alone  without  the  administration  of  any  albumin,  hut  in  tin-  case 
the  animal  is  feil  to  death.  Such  experiments  are  made  under  conditions  which 
do  not  come  into  question  in  the  ordinary  fattening  of  animals,  or  in  the 
nutrition  of  the  human  Bubject.  Apart  from  their  fodder,  the  manner  of  life 
of  the  animal-  ha-  a  greal  influence  upon  the  accumulation  of  fat.  and  espe- 
cially the  prevention  of  too  great  activity.  It  ha-  I n  determined  by  numer- 
ous and  careful  experiment-  that  sheep  and  oxen  winch  have  been  fattened 
may  he  kepi  very  fat  for  several  month-  on  a  comparatively  small  amount  of 
fodder  if  they  are  prevented  from  active  body  movements  and  protected  from 
cold.  Bul  we  should  by  no  mean-  infer  from  this  evidence  that  in  the  devel- 
opment <>]'  human  obesity  too  little  muscular  activity  is  the  only  important 
faciei-,  even   if  we  suppose  that    the   fattening  of  animals  may  he  regarded 

parallel  with  the  development  of  obesity  in  man.  of  which  however  there 
can  In-  im  doubt.  Of  course  we  know  that  active  muscular  labor  counteracts 
a  iee  profuse  accumulation  of  fat.  Bunge  believes  that  it  is  quite  healthful 
and  normal  fur  man  to  eat  everything  that  he  like-  and  in  any  quantity  that 
he  pleases,  and  that  in  an  otherwise  Hernial  mode  of  life  tin-  never  lead-  to 
obesity.  Bunge  even  declares  it  to  he  a  portentous  error  to  leek  for  the  cause 
of  obesity  in  an  over-profuse  intake  of  Dourishment  er  even  in  unsuitable  feed. 
i.e..  in  the  teo  profuse  intake  of  carbohydrates  and  fat.  But  his  ideas  by  no 
means  correspond  with  the  fact-.  Bunge,  it  is  true,  doc-  not  deny  that  differ- 
ent persons  are  predisposed  to  obesity  from  different  causes.  This  well-known 
fact  need  not  even  here  be  discussed  in  detail.  But  the  familiar  family  pre- 
disposition to  obesity  cannot  he  adduced  a-  a  proof  of  Bunge'a  assertions. 
The  objection  is  too  obvious  that  laziness  and  an  indisposition  to  take  sufficient 
muscular  exercise  are  also  family  trait-,  and  also  hereditary,  and  these  may 
lie  more  important  than  any  predisposition  to  a  too  profuse  fat  deposit.     An 


154  OBESITY 

incontestable  proof  that  a  predisposition  to  obesity  exists  may  be  seen  in  the 
fact  that  there  are  many  persons  who  eat  whatever  and  as  much  as  they  wish, 
and  nevertheless  do  not  become  obese.  In  what  this  predisposition  to  obesity 
consists  is  very  difficult  to  say.  I  look  upon  obesity,  gout,  and  diabetes  mel- 
litus as  well,  as  forming  a  single  group  of  interrelated  diseases  whose  basis 
I  designate  as  "  a  general  disease  of  protoplasm  resting  on  a  hereditary  pre- 
disposition." The  epithet  "  hereditary  "  is  not  to  be  strictly  construed.  The 
predisposition  may,  but  need  not,  be  hereditary.  By  protoplasm  I  understand 
not  only  the  cell  body  but  also  the  cell  nucleus,  therefore  the  cell  in  toto. 
One  may  readily  conceive  that  in  the  production  of  each  of  the  three  diseases 
just  mentioned  cell  body  and  cell  nucleus  are  implicated  in  different  ways, 
but  I  shall  not  follow  these  hypotheses  any  further  at  present.  The  investi- 
gations so  far  published  regarding  the  respiratory  interchange  of  gases  in  the 
obese  do  not  justify  any  definite  and  certain  opinions,  but  we  may  assume 
that  the  consumption  of  fat  in  a  person  predisposed  to  obesity  is  slighter  than 
in  one  not  so  predisposed  provided  both  live  under  the  same  conditions.  Fur- 
ther investigations  into  the  respiratory  interchange  of  gases  in  the  obese  made 
with  the  large  Pettenkofer  respiratory  apparatus,  and  lasting  longer  than 
twenty-four  hours,  are  much  needed.  Experiments  of  shorter  duration  do  not 
justify  us  in  forming  any  opinion. 

The  predisposition  to  obesity  may  become  apparent  at  any  time  in  the 
patient's  life,  and  the  manifestations  vary  much  in  intensity.  Bunge  believes 
that  there  is  no  predisposition  to  obesity  which  cannot  be  overcome  by  muscu- 
lar activity.  Whether  this  assumption  be  correct  can,  of  course,  never  be 
proven  with  certainty.  In  my  opinion  there  are  cases  which  cannot  be  cured 
by  exercise  unless  there  is  also  a  limitation  of  the  ingestion  of  nourishment. 
The  predisposition  to  obesity  rarely  shows  itself  in  childhood  to  any  unbecom- 
ing degree.  I  have  already  mentioned  that  even  in  utero  and  in  the  first 
years  of  life  there  is  normally  a  certain  plumpness  which  rarely  increases  so 
as  to  exceed  physiologic  limits.  I  have,  however,  seen  several  exceptions  to 
this  rule.  Occasionally  children  with  a  monstrous  development  of  fat  are 
exhibited  in  shows.  What  I  have  seen  of  these  makes  me  believe  that  in  cases 
of  this  kind  there  is  an  excessive  development  of  the  whole  body,  a  sort  of 
gigantism,  rather  than  a  pure  lipomatosis  universalis,  although  the  latter  is 
favored  by  their  very  unnatural  mode  of  life,  for  they  pass  their  time  almost 
exclusively  in  a  sitting  posture,  and  eat  especially  such  food  as  decidedly  pro- 
motes the  accumulation  of  fat.  Evidently  this  so-called  polypionia  infantum 
(which,  in  many  cases  at  least,  is  associated  with  the  condition  described  by 
Schönlein,  called  chlorosis  gigantea)  is  quite  rare.  More  frequent  is  an 
abnormal  accumulation  of  fat  in  adolescents,  especially  in  women  at  the 
period  of  puberty  and  in  combination  with  various  disturbances  of  menstrua- 
tion. In  boys  also,  when  the  normal  development  of  the  sexual  organs  at  the 
time  of  puberty  is  retarded,  an  increased  development  of  the  body  fat  is  not 
infrequently  noted.  That  eunuchs  are  fatter  than  normal  beings,  although 
often  maintained,  appears  to  me  to  be  insufficiently  proven.  In  animals,  how- 
ever, castration  favors  fattening.  On  the  other  hand,  there  can  be  no  doubt 
that  women  who  were  previously  thin,  after  several  labors,  very  frequently 


SYMPTOMATOLOGY  155 

even  after  their  first  child,  acquire  a  decided  increase  of  their  panniculus 
adiposis.  The  same  also  occur-  at  the  menopause,  and  during  the  period  of 
involution  in  woman.  In  some  men  we  note  that  the  body  fat  may  incn 
enormously  even  during  vigorous  adult  life.  There  can  be  no  doubt  that  at 
this  period  an  improper  mode  of  life  decidedly  favors  the  accumulation  of  fat. 
Any  one  who  goes  to  Munich,  and  watches  the  inhabitants,  will  be  able  to 
confirm  this. 

Of  special  interest  is  the  previously  mentioned  obesity  of  women  in  the 
involution  period,  which,  however,  is  by  no  means  an  invariable  occurrence, 
but  is  observed  in  only  about  one  woman  in  four  during  the  menopause. 
Nevertheless,  the  obesity  of  women  at  this  age  has  almost  become  proverbial. 
One  speaks  of  "matronly  proportions/'  and  the  Germans  have  a  yet  more 
significant  phrase,  "  fat  as  an  old  woman."  It  is  often  asserted  that  this 
accumulation  of  fat  is  due  to  the  cessation  of  menstruation,  to  the  absence  of 
function  of  the  sexual  glands  which  causes  a  decidedly  diminished  consump- 
tion of  oxygen,  and  also  thai  the  decreased  interchange  of  gases  can  be  restored 
to  normal  and  more  than  normal  in  a  comparatively  brief  -pace  of  time  by  the 
use  of  oöphorin.  which  compensates  for  the  absence  of  ovarian  activity.  Fur- 
ther investigations  will  show  whether,  and  how  far,  this  teaching  is  justified. 
At  any  rate  this  much  is  certain,  that  a  decided  increase  of  body  fat  above  the 
normal  is  often  observed  without  Lesions  of  any  special  organ  showing  a 
decidedly  determinable  influence.  Tim-,  for  example,  obesity  may  occur  after 
recovery  from  severe  illness,  and  is  then  usually  explained  by  the  long  resl 
in  bed  during  convalescence,  and  by  the  increase  of  nourishmenl  above  the 
normal  after  a  long  period  of  semi-starvation.  We  know  that  not  infre- 
quently, after  recovery  from  severe  enteric  fever,  the  patient  becomes  quite 
stout,  and  that  the  corpulence  acquired  in  tin-  way  i-  often  permanent. 

A  factor  of  importance  in  the  pathogenesis  of  obesity  is  Ihr  use  of  alcohol. 
I  have  already  referred  to  the  immoderate  use  of  beer  in  Munich,  ami  it  is 
not  necessary  to  quote  further  examples.     Bunge  also  declares  alcohol  to  he 

conducive  to  the  accumulation  of  fat.  and  in  the  main  explains  this  by  suppos- 
ing that  alcohol,  by  it-  paralyzing  action  upon  the  brain,  make-  people  lazy 
and  unwilling  to  exert   themselves. 

SYMPTOMATOLOGY 

In  discussing  the  symptomatology  of  obesity  I  -hall  follow  the  division  of 
obesity  into  three  stages  as  proposed  by  me:  if  not  pushed  to  a  pedantic  ex- 
treme, tin-  plan  simplifies  matters  very  much,  for  practical  purposes  this 
division  into  three  stages  has  Bhown  it-elf  to  be  very  serviceable.  In  the 
fir-t  stage  the  obese  man  i-  an  enviable  person,  in  the  second  a  ludicrous  one. 
ami  in  the  third  a  pitiable  one. 

The   FIRST   STAGE  mav   be   identified   with   polysorcia.      The  flesh,  the  mus- 

cles,  increase  in  due  proportion  to  the  fatty  tissue.  This  i<  the  t                esity 

which  conveys  a   majestic  impression.     The  body  becomes   fuller,  the  figure 

fill-  out.  the  per-on  reaches  a  proper  embonpoint.  Thi-  type  i-  usually  found 

in  young  persons  whose  youth  i-  full  of  activity.  In  tin-  stage  obesity 


156  OBESITY 

not  give  rise  to  any  inconvenience,  and  so  long  as  the  affected  individuals 
maintain  good  muscular  power  no  attempt  should  be  made  to  remove  or  reduce 
the  accumulation  of  fat.  A  certain  amount  of  fat  is  a  good  reserve  fund  in 
time  of  need,  for,  not .  infrequently,  even  in  this  stage  of  corpulence,  such 
unwelcome  complications  as  gout  and  diabetes  mellitus  appear.  Therefore,  in 
this  stage  of  obesity  the  condition  is  not  to  be  combated,  but  any  increase  of 
it  must  be  prevented. 

The  conditions  are  naturally  different  when  the  obese  individual  becomes 
a  ludicrous  figure.  Such  persons  suffer  from  the  ridicule  of  their  companions, 
and  form  an  excellent  subject  for  the  gibes  of  artists  and  poets.  The  portly 
Silenus  has  already  been  mentioned.  The  fat  Falstaff,  the  popular  repre- 
sentative of  low  comedy,  has  been  glorified  and  immortalized  by  no  less  a  one 
than  Shakespeare.  Not  equal  to  bodily  exercise  on  account  of  their  great 
weight,  obese  persons  in  this  second  stage  have  difficulty  in  dragging  them- 
selves along  even  upon  a  level,  and  upon  the  slightest  bodily  exertion  they  not 
only  sweat  profusely,  but,  as  a  rule,  they  must  soon  moderate  or  altogether  give 
up  their  exercise  on  account  of  dyspnea.  So  far,  however,  the  dyspnea,  though 
it  occurs  upon  slight  bodily  movement,  is  usually  still  of  the  "  functional " 
type,  i.  e.,  it  is  not  due  to  irreparable  changes  of  the  thoracic  organs  or  to  other 
gross  organic  lesions.  The  difficulty  in  breathing  is  clue  rather  to  dispro- 
portionate development  of  the  abdominal  cavity  in  which  the  enormous  dis- 
tention of  the  intestines  by  feces  and  gases  due  to  atony  of  the  bowel  plays 
no  insignificant  role.  Owing  to  this  abdominal  distention  the  thoracic  space 
is  decidedly  narrowed.  The  diaphragm  is  forced  up  and  its  free  excursion  hin- 
dered, while  the  thoracic  organs  suffer  a  more  or  less  decided  compression  lim- 
iting their  function.  Such  obese  persons,  despite  their  difficulty  in  moving, 
show  considerable  fondness  for  all  kinds  of  sport  (hunting,  horseback  riding, 
etc.),  particularly  as  they  hope  thereby  to  regain  their  health.  But  their 
motions  and  their  whole  appearance,  which  has  so  frequently  been  described 
and  put  into  song,  are  so  ludicrous  that  they  provoke  laughter.  Yet  we  must 
not  forget  that  even  at  this  stage  the  complications  and  results  of  the  immod- 
erate accumulation  of  body  fat  often  become  alarming. 

In  the  third  stage  of  obesity  all  the  severe  sequelae  develop  which  make 
the  patient  pitiable,  and,  in  fact,  he  is  commiserated.  At  this  stage  we  meet 
especially  the  symptoms  of  severe  disease  of  the  heart,  which  I  have  just 
referred  to,  as  a  frequent  accompaniment  of  obesity.  This  gives  rise  to  dysp- 
nea due  to  severe  anatomical  changes  in  the  heart,  and  thus  differing  from  the 
functional  form  above  described.  Besides  this,  a  constant  accompaniment  of 
every  case  of  marked  obesity  is  a  steadily  increasing  anemia.  Prominent 
observers  have  contrasted  the  anemic  form  of  obesity  with  a  plethoric  variety, 
but  appearances  are  deceptive.  I  need  only  mention  the  obese  chlorotics  from 
the  country  with  their  very  red  cheeks.  Even  if  we  admit  the  possibility  of 
plethora  vera  seu  sanguinea  (which  in  fact  is  a  greatly  disputed  condition), 
we  must  specifically  deny  that  any  plethora  occurs  in  well -developed  obesity. 
Plethora  could  only  happen  in  those  forms  of  corpulence  which  belong  to 
the  first  stage  of  the  disease,  i.  e.,  that  in  which  the  muscular  system  is 
still  in  a  normal  condition.     In  general,  anemia  with  all  of  its  symptoms 


SYMPTOMATOLOGY  157 

and  consequences  is  typical  of  advanced   obesity,  especially  of   Lipomatosis 
universalis. 

We  have  already  said  that  the  other  general  "diseases  of  protoplasm  based 
on  hereditary  predisposition''  (pout  and  diabetes  mellitus),  frequently  com- 
plicate the  earlier  stages  of  obesity,  the  enviable  and  the  ludicrous  stages. 
These  unfortunate  complications  should  not  be  regarded  as  direel  sequelae  of 
obesity,  but  as  diseases  developed  as  the  result  of  a  pathologic  condition  of  the 
body  cells.  The  three  diseases  need  not  accompany  or  follow  one  another,  but 
may  arise  independently.  Hence  we  must  infer  that  in  each  of  them  a  sepa- 
rate abnormality  of  protoplasm  exists.  That  uratic  calculi  often  occur  in 
the  form  of  obesity  which  is  commonly  seen  in  combination  with  gout,  and 
that  the  -tones  are  caused  by  the  pout,  has  been  taught  me  often  enough  by 
my  own  experience.  These  stones  rarely  reach  such  a  size  that  they  cannot 
be  spontaneously  voided  with  the  urine. 

Atheromatous  degeneration  of  the  arteries,  which  is  not  infrequently  noted 
in  combination  with  obesity.  1  should  not  so  much  refer  to  the  obesity  as  to 
the  often  coexisting  pout,  thai  is,  to  the  uric  acid  diathesis.  The  obese,  as  a 
rule,  enjoy  an  excellent  appetite.  Almost  invariably  they  eat  more  than  nor- 
mal persons  under  otherwise  similar  conditions.  Special  stress  is  to  be  laid 
upon  this  in  estimating  the  quantity  of  food  which  a  corpulenl  individual 
consumes.  Naturally  we  must  not  depend  upon  his  own  reports.  In  my 
experience  obese  individuals  who  are  recognized  as  notorious  gourmands,  will, 
if  questioned,  deny  that  they  consume  an  immoderate  amount  of  food.    They 

usually  only  say  that  their  food  agrees  with  them  very  well.     Fat  | pie  often 

have,  as  I  have  already  pointed  out,  a  tendency  to  obstinate  constipation. 
Hemorrhoids  exist,  or  at  leasl  develop,  very  often.  Upon  the  basis  of  the 
composition  of  the  urine,  A.  Robin  has  differentiated  two  forms  of  obesity. 
In  the  one  form  there  is  profuse,  in  the  other  very  slight,  excretion  of  urea 
and  phosphates.  Robin  believes  that  in  the  former  group  obesity  is  the  result 
of  increased,  in  the  latter  case  of  decreased,  assimilation.  He  holds  that  this 
division  is  of  greal  importance,  especially  in  measuring  the  amount  of  fluid 
allowed  in  the  dietetic  treatment.  Thai  with  the  previously  mentioned  com- 
plications the  urine  shows  corresponding  changes,  need  only  be  indicated  here. 
In  advanced  obesity  there  is  usually  a  tendency  i<>  catarrhal  conditions,  espe- 
cially of  the  pharynx  and  of  the  bronchia]  tree. 

Obesity,  if  left  to  itself  (or  improperly  treated),  and  when  no  conditions 
arise  which  produce  emaciation — as,  for  example,  severe  acute  or  chronic 
affections  becomes  a  protracted  disease  which,  as  a  rule,  -how-,  a  tendency  to 
progress.  Ye\  I  have  not  infrequently  known  persons  who  have  become  fat 
in  middle  age  to  lose  their  f,-it  as  they  grew  older  without  an  apparent  reason, 
usually  tins  is  not  the  case.  As  regards  longevity,  obesity  is  a  factor  gener- 
ally considered  to  shorten  life.  On  this  point  we  are  indebted  to  the  life 
insurance  companies  for  valuable  conclusions.  Especially  worthy  of  note, 
it  appear-  to  me,  i-  w  hat  A.  Eägler  says  in  his  hook  "  <  >n  the  factor-  of  Resist- 
ance and   the   Prog is  of  the   Duration  of   Life  in    Normal    Individuals" 

(Basel,  1896,  page  \',  e\  seq.)  regarding  the  prognosis  op  obesity.  All 
cases  are  by  no  means  to  be  judged  by  the  same  scale.     A.ge,  heredity,  manner 


158  OBESITY 

of  life  and  occupation  must  be  carefully  considered.  Moreover,  we  should 
ascertain  the  patient's  power  of  reaction  against  external  influences,  especially 
mountain  climbing  and  other  bodily  exercise.  Hägler  requires  that  obese 
persons  with  an  apoplectic  or  a  diabetic  family  predisposition,  with  irregular 
pulse,  with  decided  bradycardia,  those  who  live  in  an  improper  manner,  and 
those  who  are  addicted  to  the  use  of  alcohol,  should  be  excluded  from  life 
insurance.  No  absolute  norm  for  a  maximal  or  minimal  body-weight  exists, 
but  the  rules  laid  down  by  Hägler  are  nevertheless  noteworthy :  "  The  insur- 
ance company  at  Basel  is  very  cautious  in  its  dealing  with  individuals  of  less 
than  340  grains,  or  more  than  530  grams  of  weight  per  centimeter  of  body- 
height,  and  such  are  usually  rejected.  We  have,  however,  reached  the  con- 
clusion that  in  certain  regions,  especially  among  the  very  large,  often  giant- 
sized,  land  owners  and  farmers  of  East  Friesland,  a  higher  body-weight  is 
compatible  with  a  normal  duration  of  life."  In  my  professional  activity  I 
have  come  across  such  persons,  and  in  general  may  confirm  this  statement. 
But  however  true  this  may  be,  the  risk  of  the  obese  person  is  to  be  estimated 
with  caution.  Even  the  enviable  stage  of  obesity  I  look  upon  with  suspicion, 
for  it  happens  now  and  then  that,  without  the  ludicrous  intervening,  the 
pitiable  stage  arises,  and  this  is  especially  frequent,  in  my  experience,  in  the 
cases  in  which  obesity  is  associated  with  diabetes  mellitus.  Primary  arthritic 
gout,  even  when  it  runs  a  severe  course,  produces,  as  I  have  seen,  far  less  dele- 
terious effects.  Frequently  the  obese  are  threatened  by  lesions  of  the  heart 
and  the  vascular  system.  In  the  heart  itself  in  consequence  of  fatty  deposits 
dilatation  at  first  develops;  sooner  or  later,  when  compensation  for  the  dam- 
age to  the  cardiac  muscle  is  no  longer  possible,  the  symptoms  of  muscular 
insufficiency  supervene.  The  vascular  disturbances  are  scarcely  dependent 
upon  obesity,  but  are  to  be  referred  to  the  uric  acid  diathesis,  usually  a  factor 
in  such  cases.  The  arterial  diseases  of  the  obese  usually  cause  effusions  of 
blood  into  the  brain,  to  which  many  fat  persons  succumb.  It  is  of  great 
practical  importance  in  prognosis  that  persons  who  suffer  from  obesity,  as  is 
proved  by  experience,  readity  succumb  to  any  infectious  disease  that  attacks 
them.  Among  other  factors  which  render  the  prognosis  more  serious  in 
obesity,  I  must  particularly  emphasize  the  fact  that  as  it  progresses  it  makes 
the  affected  individual  more  and  more  sedentary,  a  habit  to  which  the  foot 
affections  arising  as  the  result  of  obesity  also  furnish  their  share.  Flat-foot 
very  often  develops  in  the  young,  particularly  in  individuals  hereditarily  pre- 
disposed to  obesity,  when  the  body-weight  increases.  This  usually  affects 
those  belonging  to  the  higher  classes  of  society,  men  as  well  as  women.  I 
should  like  to  add  here  that  I  have  observed  such  cases  of  flat-foot,  mostly  in 
those  with  a  gouty  predisposition.  This  is  particularly  worthy  of  note  because 
such  a  deformity  of  the  foot  cannot  be  cured  without  considering  gout  as 
an  etiologic  factor.  A  sufficient  amount  of  active  muscular  exercise  is  quite 
impossible  on  account  of  the  affection  of  the  joints  of  the  foot  and  the  result- 
ing pain.  But  if  the  superfluous  fat  is  removed  by  suitable  dietetic  regimen, 
with  the  slighter  weight  the  diseased  feet  will  also  show  a  corresponding 
improvement. 

At  this  point  some  remarks  on  the  influence  of  increasing  obesity  upon 


DIAGNOSIS  159 

the  psychical  life  of  the  patient  may  be  in  order.  It  is  commonly  believed 
that  fat  persons  have  a  more  phlegmatic,  and,  associated  with  this,  an  espe- 
cially good-natured  disposition.  That  there  is  a  necessary  connection  between 
obesity  and  a  special  temperament  characterized  by  Indifference  and  apathy  is 
certainly  not  true.  I  wish  to  issue  a  warning  again-t  the  adoption  of  this  very 
common  assumption  as  correct.  [That  this  is  the  general  view,  not  only 
among  the  laity  but  even  among  philosophers  and  poets,  is  well  illustrated  by 
tin'  familiar  quotation  from  Julius  Caesar,  Act  1,  Scene  II,  lines  192,  et  seq.: 

Let  me  have  men  about  me  that  are  fat. 

Sleek-headed  men,  and  such  as  sleep  o'  nights: 

Yon   <'a--ius   has   a   lean  and  hungry  look; 

He   thinks  too   much:    such   men   are    dangerous.  (J.  L.  S.)] 

It  is  true,  however,  that  the  obese  individual  is  usually  distinguished  by  a 
less  irritable  nervous  system.  It  is  often  declared  that  obesity  hinders  the 
development  of  great  mental  power.  With  necessary  limitation-,  we  mu-t 
admit  the  truth  of  this  assumption  as  regards  the  extreme  types  of  obesity. 
One  who  has  a  great  burden  of  body  fat  to  carry  about  with  him  can  hardly 
be  expected  to  develop  mental  powers  equal  to  those  of  persons  not  limited  in 
this  way.  So  long-  as  obesity  is  not  excessive,  strong,  energetic,  and  talented 
natures  will  be  able  to  adjust  themselves  to  the  increase  of  their  body  fat  and 
the  resulting  restriction  of  their  bodily  movements  without  suffering  any  con- 
siderable limitation  of  their  mental  functions. 


DIAGNOSIS 

The  diagnosis  of  obesity  is.  as  a  rule,  made  correctly  by  the  laity,  for  the 
condition  i-  obvious,  and  may  be  determined  whenever  one  finds  an  immoderate 
development  of  fat  in  the  subcutaneous  connective  tissue.  More  perplexing 
i.-  the  decision  whether  the  superfluous  tat  development  ha-  proven  detrimental 
to  other  structures,  for  example,  to  the  muscular  tissue,  as  we  should  assume 
in  all  of  the  more  marked  grade-,  of  obesity.  Hut  I'm-  the  physician  thi-  offers 
no  great  difficulty.  Whether  too  much  fat  is  formed  and  deposited  in  the 
area-  of  the  subcutaneous  connective  tissue  which  are  mosi  accessible  to  exami- 
nation is  readily  learned  in  mosl  cases  by  observation  of  those  part-  of  tin' 
body  not  covered  by  clothing,  particularly  the  face.  The  cheek-,  and  espe- 
cially the  region  of  the  chin,  appear  more  ma  —  ive  than  normal.  The  "  double 
chin"  is  a  familial-  feature.      Yet    there  are  fat    individuals  in  whose  face-  the 

fat  doe-  not  reach  decided  proportions.  The  nude  body,  as  a  rule,  -how-  accu- 
rately to  what  extent  fa1  ie  accumulated  in  the  subcutaneous  connective  tissue. 

All  the  landmark-  of  the  body  are  displaced  in  obesityj  they  appear  a-  i  I'  they 
had  been  forced  downward  or  pushed  laterally.  There  18  great  accumulation 
of  fat  in  the  subcutaneous  tissue  of  the  mammary  region,  not  only  in  fat 
women  but  also  in  fat  men;  in  the  latter  we  often  see  the  subcutaneous  fat 
heap  up  until  it  produces  masses  that  in  point  of  -i/e  are  qoj  much  le~s  than 

the  well-developed  female  mamma.  I'pon  the  abdominal  walls  thick  Iran-- 
ver-o  roll,  of  fat    may  often  he  aeen.      Upon   the  lower  portions  of  the  thorax. 


160  OBESITY 

and  particularly  over  the  crests  of  the  ilium,  groat  collops  of  fat  stand  out. 
An  enormous  size  is  often  attained  by  the  buttocks  which  are  thickly  cushioned 
with  fat.  These,  however,  do  not  appear  rounded  but  assume  a  somewhat 
triangular  form  since  the  masses  of  fat  hang  downward  and  deviate  laterally. 
Over  the  fold  of  the  buttocks  there  is,  therefore,  a  thick,  shapeless  mass  formed 
by  the  superficial  subcutaneous  fatty  tissue,  which  projects  considerably  beyond 
the  lateral  line  of  the  thighs.  In  other  cases  the  fat  accumulates  particularly 
in  the  sacral  and  lumbar  regions.  The  remarkably  great  development  at  the 
fold  of  the  buttock  continues  downward  into  the  upper  portion  of  the  thigh, 
where  the  subcutaneous  fatty  tissue  shows  an  increase  that  is  scarcely  less  con- 
spicuous. In  very  corpulent  persons  the  subcutaneous  fatty  tissue  upon  the 
legs  also  forms  prominent  tumors.  Of  course,  it  is  only  at  the  autopsy  of  the 
obese  that  we  can  recognize  the  full  extent  of  the  enormous  masses  of  fat  which 
pack  the  internal  cavities  of  the  body,  the  mediastinal  fat,  the  fat  upon  the 
pleura,  the  great  accumulations  of  epicardial  fat,  the  often  excessive  accu- 
mulation of  fat  in  the  omentum  and  mesentery,  as  well  in  the  folds  of  the 
synovial  membranes,  etc. 

J.  P.  Frank  mentions  a  man  observed  by  Boerhaave  who,  as  the  result  of 
over-indulgence  in  food  and  drink,  became  so  fat  that  the  abdomen  had  to  be 
carried  in  a  sling  which  reached  down  from  the  shoulders,  and  the  table  at 
which  he  was  accustomed  to  sit  had  to  be  cut  away  in  a  semicircle.  His 
mesentery  alone  weighed  33  pounds. 

Such  fat  people  are  generally  looked  upon  as  unsightly.  Among  the 
Moors,  however,  obesity  in  women  is  regarded  as  a  great  mark  of  beauty,  and 
among  the  Kelowi  in  Central  Africa  a  faultless  odalisk  must  have  the  weight 
and  circumference  of  a  young  camel,  a  circumference  which  she  attempts  to 
secure  by  a  fattening  process  carried  out  with  great  perseverance.  De  gustibus 
non  est  disputandum ! 

I  have  already  mentioned  the  conclusions  of  the  Basel  Life  Insurance 
Company  in  regard  to  the  proportion  between  size  and  body- weight  as  a  factor 
in  prognosis.  In  the  diagnosis,  however,  we  must  determine  not  only  that 
the  individual  in  question  is  obese  but  also  the  degree  of  his  obesity;  we  must 
recognize  probable  complications  and  the  patient's  capacity  for  work  ;  we  must 
decide  to  what  extent  he  is  anemic,  etc.  All  these  questions  must  be  accu- 
rately determined  before  treatment  is  begun,  and  careful  examination  of  the 
urine  must  be  made  in  every  case  if  gross  errors  are  to  be  avoided. 

TREATMENT 

The  treatment  by  which  a  patient  is  freed  from  his  fat  is  often  designated 
antifai  treatment.  Of  course,  the  individual  is  not  to  be  rid  of  all  his  fat 
and  reduced  to  absolute  leanness,  but  he  is  to  have  the  surplus  fat  removed. 
In  such  an  antifat  treatment,  it  must  never  be  forgotten  that  adipose  tissue 
is  a  normal  constituent  of  the  body,  and  that  its  complete  absence  is  not  only 
unbecoming  but  a  decided  menace  to  the  health  of  the  person  in  question. 
There  are  people  whose  occupation  necessitates  that  they  lie  thin  and  remain 
so,  guarding  themselves  against  the  over-accumulation  of  fat  from  any  cause. 


TREATMENT  161 

This  is  attained  by  a  process  of  training,  so  called,  which  consists  in  systematic 
and  gradually  increased  exercise  combined  with  a  suitable  diet.  In  this  man- 
aer  such  persons  fit  themselves  for  various  feats  of  strength.  There  is  special 
training  for  riding,  for  marching,  for  swimming,  for  rowing,  etc.     Wo  are 

all  familiar  with  the  i raining  of  race  horses;  by  a  special  kind  of  treatment. 
by  feeding  and  systematic  muscular  exercise,  they  are  prepared  for  their  task. 
By  the  same  means  men  may  prevent  an  increase  of  obesity,  and  eventually 
even  become  rid  of  it.  In  the  well  known  processes  of  training,  therefore,  the 
first  principles  of  the  treatment  of  obestfy  are  embodied.  Nevertheless  the 
detailed  application  of  the  latter  is  decidedly  different,  in  that  such  tests  of 
strength  as  are  used  in  training  are  not  suitable  in  the  treatment  of  obesity, 
and.  as  a  rule,  would  he  dangerous  in  a  corpulent  person. 

Nothing  is  easier  than  to  make  a  person  lean.  Debove  at  a  meeting  "f 
the  Academic  de  Medecine  at  Paris  on  the  6th  of  March.  1900,  showed  a  patient 
who  had  just  passed  through  an  emaciation  rare  (cure  d'amaigrissement). 
T<>  explain  this  method  I  will  quote  briefly  a  review  of  Debove's  treatment 
published  in  the  Semaine  Medicate,  No.  10,  1900,  showing  what  this  physician 
advises  in  the  treatment  of  obesity. 

I  must  remark  at  the  outset  that  obesity  cures  and  emaciation  cure-  are 
by  no  means  to  be  looked  upon  as  synonymous.  In  the  former  only  the  .super- 
fluous fat  is  to  he  removed,  while  in  the  latter  both  fat  and  muscle  are  to 
he  diminished.  Leanness  is  attained  by  hunger;  a  treatment  to  produce  lean- 
no--,  and  a  hunger  cure  are  identical.  Debove's  obese  patient,  who  suffered 
from  urinary  gravel,  weighed  before  treatment  (which  la-ted  less  than  a  year), 
1  IT  kilogram-;  after  treatment  he  weighed  only  '.» 1  kilograms.  The  patient. 
therefore,  in  less  than  a  year  lost  53  kilograms  of  body-weight.  How  was  this 
attained?  The  patient  was  put  upon  a  pure  milk  diet.  He  received  daily 
for  one  month  '!\  liter-  of  milk,  during  the  second  month  only  *-2  liters,  and 
in  the  third  month  only  one  liter  per  day.  The  patient,  who  was  unable  to 
leave  his  bed,  lo-t  in  the  first  two  months  of  tin-  treatment  15,  and  in  the 
third  month  .">,  kilograms  of  body-weight.  After  the  first  three  month-  he 
weighed  only  127  kilograms.  During  the  next  loin'  month-  tin'  patient  re- 
ceived daily  only  one  I  iter  of  milk.  At  I  he  end  of  -even  month-  from  the  begin- 
ning of  the  treatment  he  weighed  only  105  kilograms.  II«'  then  ceased  to 
emaciate.      Hut    after  a   change  of  diet    which    permitted    the   patient    to   take 

cooked  vegetables,  salad  and   fruit   in  any  quantity  that   he  desired,  he  lo-t 

12  kilogram-  more.  SO  that  he  then  weighed  only  9  I  kilograms.  A-  the 
result  of  thi-  treatment  Debove  report-  that  the  man  not  . . 1 1 1 \  \va-  re- 
duced in  flesh  hut  that  he  regained  his  health  and  his  physical  and  moral 
capacity.  Debove  hope-  thai  the  good  effects  of  tin-  treatment  will  be 
maintained. 

Thi-  ca-e  demonstrates  that  occasionally,  by  mean-  of  a  starvation  cure, 
we  may  obtain  good  results.  In  tin-  case  there  was  certainly  a  considerable 
degree  of  malnutrition,  for  •.'..">  liter-  of  milk  per  day.  the  amount  which  the 
patient  received  for  the  first  month,  i-  decidedly  insufficient  for  nutrition,  t<> 

say  nothing  of  the  fact  thai  he  had  to  content  himself  for  month-  with  one  liter 

a  dav.     Now  it  i-  certainly  strange  that,  in  this  patient,  loss  of  weight  ceased 


162  OBESITY 

after  seven  months  in  spite  of  continued  insufficient  nourishment.  On  the 
other  hand,  upon  administration  of  a  purely  vegetable  diet,  especially  after 
partaking  of  fruit  in  unlimited  quantity,  loss  of  weight  again  took  place.  I 
can  only  explain  these  facts  by  supposing  that  the  patient,  after  the  first 
seven  months,  became  so  hydremic  that  a  further  loss  of  weight  was  no  longer 
possible.  Subsequently,  a  decrease  in  weight  could  only  be  brought  about 
when,  by  the  diuretic  influence  of  the  vegetable  acid  salts  resulting  from  the 
ingestion  of  large  quantities  of  fruit,  depletion  of  the  fluids  of  the  body 
occurred. 

In  obesity  cures  nowadays  we  naturally  do  not  wish  to  use  any  method  of 
treatment  which  brings  about  inanition.  It  is  true  that  in  every  obesity  cure, 
however  rationally  it  is  carried  out,  there  must  always  be  depletion  of  some 
kind.  This  depletion,  however,  must  not  go  so  far  that  muscle  as  well  as  fat 
is  lost.  A  withdrawal  of  fat  without  loss  of  muscle  can  be  brought  about  by 
a  suitable  change  in  the  diet  or  by  increased  muscular  activity,  or — best  of 
all — by  a  combination  of  both  methods.  By  a  diminution  of  the  nourishment 
which  has  previously  been  taken  in  excess,  and  by  an  increase  of  muscular 
exercise  which  has  previously  been  insufficient,  the  superfluous  body  fat  will 
gradually  be  consumed.  I  do  not  doubt  for  a  moment,  and  I  have  often  em- 
phatically said,  that  this  goal  may  be  reached  by  very  simple  means.  Typical 
in  this  respect  is  the  quaint  tale  of  Johann  Peter  Hebel,  which  many  an  indo- 
lent, fat  carouser  may  take  as  an  example.  This  story  is  told  of  a  rich,  fat 
Amsterdamer,  whose  physician,  living  a  hundred  hours'  journey  from  him — 
and  this  was  no  less  a  personage  than  the  celebrated  physician  Boerhaave,  of 
Leyden — insisted  that  the  patient  visit  him,  and  that  he  come  on  foot.  He 
impressed  upon  him  the  necessity  of  a  regular  mode  of  life  in  order  to  crush 
the  dragon  which  he  carried  around  in  his  abdomen.  The  patient  became 
an  expert  pedestrian,  and  then  learned  to  saw  wood;  he  restricted  himself  to 
the  food  that  hunger  required,  became  as  healthy  as  a  fish  in  water,  and  reached 
the  age  of  eighty-seven  years,  four  months  and  eighteen  days.  These  effective 
means  of  preventing  an  excessive  increase  of  body  fat,  or  of  causing  superflu- 
ous fat  to  disappear,  have  met  with  little  favor,  though  obviously  they  are  so 
easy  to  carry  out.  We  see  that  celebrated  physicians  like  Johann  Peter  Frank 
almost  maintain  an  attitude  of  hopelessness  as  regards  measures  for  the  re- 
moval of  obesity.  Frank  joins  in  the  old  complaint  of  a  Leipsic  physician 
of  his  time  that  "  a  few  succeed,  by  the  aid  of  very  strict  diet,  in  wholly  ridding 
themselves  of  their  superfluous  fat;  as  soon,  however,  as  they  have  accom- 
plished this  (not  without  great  loss  of  power),  and  attempt  to  recuperate  by 
a  less  severe  nutrition  and  mode  of  life,  they  regain  their  previous  amount  of 
fat,  or,  in  its  place  are  attacked  by  a  pitiable  condition  of  dropsical  accumu- 
lation." It  is  obvious  from  this  that  J.  P.  Frank  had  starvation  cures  in 
mind,  and  that  he  was  so  daunted  by  these  unfortunate  experiences  that  he 
did  not  further  pursue  his  endeavors.  He  mentions  no  special  dietetic  rules 
for  the  relief  of  obesity. 

It  seems  to  me  best  to  present  in  chronological  order  a  comprehensive 
review  of  the  methods  of  treatment  which  have  been  employed  in  our  time, 
and  I  desire  expressly  to  state  that  much  that  has  been  claimed  by  individual 


TREATMENT  163 

authors,  with  great  self-laudation,  as  the  product  of  their  own  ingenuity,  may 
be  referred  to  very  ancient  sources. 

First,  then,  as  the  earliest  of  the  modern  methods  of  treatment  of  obesity. 
the  "no-fat  cure"  must  be  mentioned.  This  treatment  prohibits  the  eating 
of  fat,  on  the  principle  that  under  all  circumstances  fat  will  produce  fat.  The 
type  of  this  is  the  so-called  "Banting  cure."  Banting,  a  very  corpulent  Eng- 
lishman, who  lost  his  fat  by  this  method  under  the  treatment  of  his  physician, 
Harvey,  has  made  himself  and  his  cure  widely  celebrated.  Certainly  it  is  to 
his  credit  that  he  described  his  disease  and  his  treatment  in  a  very  charming 
manner.  This  made  obesity  cures  popular  for  the  first  time,  but  they  were 
in  practice  long  before  Banting's  time.  A  Parisian  physician,  Dr.  Leon,  in 
the  year  1839.  was  the  first  to  translate  and  annotate  the  work  of  the  English 
physician,  Wadd.  Tins  book  treated  of  corpulence  and  its  cure,  and  at  the 
same  time  emphasized  the  fact  that  fat  people  must  learn  to  endure  thirst  as 
much  as  possible.  Leon  appropriated  the  ancient  teaching  of  Pliny,  to  which 
I  shall  revert  later.  His  views,  however,  did  not  appear  to  meet  with  general 
approval.  Much  greater  publicity  was  attained  by  the  methods  of  the  Eng- 
lish pbysician,  Thomas  K.  «bambers.  He  prohibited  most  strictly  the  use 
of  fats  and  sugar  as  well  as  starch  in  the  form  of  potatoes;  he  limited  decid- 
edly the  eating  of  bread,  and  permitted  only  very  small  quantities  of  fluids. 

I  shall  here  quote  two  of  Chambers's  diet-tables;  it  is  obvious  that  the 
first  is  much  more  strict  than  the  second.  The  conclusion  may  be  drawn 
from  these  tables  that  the  enforcement  of  such  strict  rules  met  with  great 
opposition  on  the  part  of  the  patient.  Perhaps,  too.  Chambers  himself  found 
that  too  great  a  limitation  of  X-free  food-  is  not  well  borne  by  patients. 

1.  Thos.  K.  Chambers,  '"Corpulence  or  Excess  of  Fat  in  the  Human  Body,"  London, 
1850,  p.   126. 

Breakfast:  Dry.  toasted  bread,  or.  better,  ship  biscuit;  if  severe  muscular  exercise 
is  contemplated,  ;i  -mall  piece  of  Iran  meat  i-  also  permitted. 

Midday  meal  (one  o'clock)  :  8 e  meat  (withoui  tat  i  ;  with  this  -tale  bread  er  crack- 
ers, or  a  small  quantity  of  maccaroni  (cooked  -oft  with  some  French  mustard  or  stewed 
fruit),  or  some  pracker  pudding.    Fluids  may  only  be  taken  one-half  hour  after  a  meal. 

Later  in  the  <la\  if  a  sensation  of  weakness  appear,  a  piece  of  biscuil  ami  a  glass 
of  water,  otherwise  no  solid  food  i-  permitted:  before  ":<>ite_:  to  lied  a  cup  of  gruel  or  a 
baked  apple  is  allowed.  Chambers  believes  ten  ounces  (=300  grams)  of  solid  food  to  he 
sufficient,  hut  prescribes  a  -mall  quantity  of  malt  extract  at  mealtime  more  effectually 
to  (juiet  hunger. 

1.  Chamber  a,  "Lectures  on  Corpulence,"  London,  1864,  p.  642, 

Breakfast  (to  I"'  taken  early)  :  Two  lamb  chops  carefully  freed  from  fat.  broiled  or 
stewed,  and  ship  biscuit.     By  way  of  variation  a  pigeon,  game,  or  Bah  in  corresponding 

amount.      As    fluid:    Soda    water,   or.   even    hitter.  ordinaiv     water,   perhaps   a    cup   of    tea 

without  milk  made  in  the  Russian  style  with  a  thick  -lice  of  lemon. 

Lunch    i  second   breakfast):   The  same  solid    foods,     Fluid:   a   irla-s  of  claret   and 

Burgundy,  half  and  half,  with  water. 

Dinner  (besi  about  six  o'clock)  :  Soup  and  Ash  are  to  l»-  avoided.  Boiled  lamb  and 
beef  arc  to  form  the  principal  constituents  of  diet.  With  this  some  biscuil  with  regeta 
bles  rich  in  chlorophyl  and  Btarch,  such  a-  cabbage,  lettuce,  spinach,  beans,  and  celery 

in   small   amounts:    no   potatoes.      Sweet-,   eggs,   and    I i    an-   to   he  avoided    lil.r   poison. 

Next  to  water,  clarei  Is  the  besi  drink.    Champagne  i^  the  worst. 

\ing:  A  cup  of  tea   in  the  Russian  style,  or  a  glass  oi  ice  water,  or.  better,  a 
glass  of  soda  water  or  ordinary  water. 


164  OBESITY 

Banting's  diet  list  is  as  follows : 

Breakfast:  120  to  150  grams  of  beef  or  lamb,  kidneys,  fried  fish,  bam,  or  any  cold 
meat  (only  pork  being  absolutely  prohibited),  a  large  cup  of  tea  without  milk  or  sugar, 
some  rusks,  or  30  grams  of  toast  without  butter  (total  of  150  to  180  grams  of  solids 
and  240  grams  of  fluid). 

Besides,  Banting  first  took  a  swallow  of  "  Balsam  of  Life  " — probably  a  kind  of 
bitter-tonic. 

Midday  mail:  150  to  180  grams  of  fish  (except  salmon),  or  meat  (no  pork),  or  any 
kind  of  poultry  or  game,  all  sorts  of  vegetables  (except  potatoes),  30  grams  of  toasted 
bread  or  stewed  fruit.  Two  to  three  glasses  of  red  wine,  sherry  or  Medoc  (champagne, 
Port  wine  and  beer  are  prohibited)  ;  total  of  240  grams  each  of  fluids  and  solids. 

Afternoon:  A  cup  of  tea  (without  milk  or  sugar),  60  to  90  grams  of  fruit,  one  or 
two  large  biscuits ;  total  of  60  grams  of  solid  and  240  grams  of  fluid. 

Supper:  90  to  220  grams  of  meat  or  fish  (same  varieties  as  at  the  midday  meal), 
and  one  or  two  glasses  of  red  wine;  total  90  to  120  grams  of  solids  and  180  grams  of 
fluid.  As  a  drink  just  before  going  to  bed  some  grog  (consisting  of  red  wine  or  rum 
without  sugar)   or  one  or  two  glasses  of  red  wine. 

In  this  compilation  it  appears  that  Banting  (who  in  respect  to  quantities 
did  not  exactly  conform  to  this  scheme)  was  allowed  by  his  physician  about 
600  to  650  grams  of  solids  and  500  to  1,000  grams  of  fluid  per  day.  In 
Banting's  letter  describing  his  cure  I  cannot  find  the  statement  that  he  allowed 
an  unlimited  supply  of  water  to  persons  predisposed  to  obesity — as  Immer- 
mann and  Cantani  report. 

The  following  rules  of  Robin  may  also  be  arranged  among  the  antifat 
cures.  Albert  Robin  (Revue  de  tlierap.  med.-cliir.,  1897,  No.  24,  quoted  from 
the  Correspondenzblatt  für  Schweizer  Aerzte,  1898,  page  96,  No.  3)  permits 
five  meals  daily. 

1.  Eight  o'clock  in  the  morning:  A  soft  boiled  e^<x,  20  grams  of  fish  or  lean  meat 
taken  cold  without  any  addition,  10  grams  of  bread,  a  cup  of  weak  tea  as  hot  as  possible 
and  without  sugar. 

2.  Ten  o'clock:  Two  soft  boiled  eggs,  5  grams  of  bread,  160  c.c.  of  wine  with  water, 
or  tea  without  sugar. 

3.  Twelve  o'clock  (midday  meal)  :  Cold  meat  according  to  choice  but  without  bread; 
as  a  substitute  for  bread,  lettuce  or  water-cress  with  a  little  salt ;  if  absohitely  necessary 
at  most  30  grams  of  bread.  Exclusively  green  vegetables,  particularly  boiled  lettuce 
(100  to  150  grams).  The  same  quantity  of  raw  fruit  for  dessert;  as  fluid  one  or  two 
glasses  of  red  wine  with  water. 

A  quarter  of  an  hour  after  the  meal  a  cup  of  weak  tea  without  sugar. 

4.  Four  o'clock  p.m.:  A  cup  of  weak  tea  without  sugar. 

5.  Evening,  seven  o'clock  (supper)  :  Same  as  in  the  morning  at  eight  o'clock  with 
the  addition  of  hot  meat  with  or  without  fish,  at  most  100  grams. 

After  every  meal  a  walk  lasting  for  one-half  to  three-quarters  of  an  hour;  besides, 
general  hygienic  measures,  hydrotherapy  with  friction,  steam  baths  and  general  massage 
are  advised.  Seven  hours  of  sleep  for  adults,  eight  hours  for  children.  No  sleep  dur- 
ing the  day.  Regarding  Robin's  advice  as  to  the  amount  of  fluid,  mention  will  be 
made  later. 

Robin's  diet  regulations  require  much  greater  self-denial  on  the  part  of 
the  obese  than  those  of  the  English  authors  previously  mentioned.  I  think 
it  quite  likely  that  Robin  reckoned  first  of  all  with  the  manner  of  life  and  the 
dietetic  peculiarities  of  his  French  compatriots.     Cantani  is  more  strict  with 


TREATMENT  165 

his  obese  patients,  lie  absolutely  prohibits  not  only  all  fat,  but  also  all  foods 
made  of  flour,  and  also  all  sugar-containing  materials. 

Cantani  probably  realized  that  the  dietary  formulas  which  he  published 
could  scarcely  be  followed  by  the  obese,  or  only  endured  for  a  brief  while. 
In  some  of  his  patients,  partly  on  account  of  the  unconquerable  aversion  con- 
sequent upon  consuming  such  great  amounts  of  meat,  partly  on  account  of  the 
incapacity  of  the  stomach  to  digest  so  much  animal  food,  and  partly  because 
of  the  great  muscular  debility  which  appeared  after  following  his  dietary 
rules,  Cantani  himself  combined  his  rules  with  Harvey-Banting  formulas 
in  which  a  certain  quantity  of  carbohydrates  and  fat  were  permitted.  How- 
ever, even  the  -'»-called  Banting  cure  is  by  no  means  harmless.  The  large 
quantity  of  albumin  required  by  it  on  the  one  hand,  and  the  too  great  limita- 
tion of  X-free  foods  ( fat  and  carbohydrates  |  on  the  other  hand,  are  very  badly 
tolerated  by  the  patient,  and.  a-  professional  experience  has  shown,  not  infre- 
quently are  productive  of  serious  harm.  We  know,  for  example,  to  mention 
hut  «me  point,  that  no-fat  cures  of  this  kind  may  produce  severe  organic  dis- 
ease of  tin'  kidneys.  The  danger  of  such  cures  would  be  yel  greater  if  the 
"  lean  meat  "  did  not  contain  a  certain  proportion  of  fat:  even  lean  beef  con- 
tains aliout  2  per  cent,  of  fat.  Nevertheless,  the  amount  of  carbohydrates 
allowed  by  these  tallies  is  still  insufficient.  Cheese,  of  course,  cannot  he  taken 
in  a  no-fat  cur< — it  is  expressly  forbidden  by  Cantani — as  there  is  no  kind 
of  cheese  that  is  free  from  fat. 

By  this  no-fat  method  of  treatment,  quite  insupportable  conditions  are 
produced  which  even  a  very  strong-willed  person  can  at  mosl  endure  for  only 
a  brief  while.  Yet  these  method-,  were  those  mosl  commonly  employed  up  to 
the  beginning  of  the  eighth  decade  of  the  nineteenth  century.  Since  then, 
however,  the  "no-fat"*  method  has  more  and  more  fallen  into  disuse.  Of 
course,  it  inu-t  lie  admitted  that  the  treatment  by  the  withdrawal  of  fat  is 
effectual  and  even  to  a  certain  degree  rational,  i.  <■..  by  such  a  system  of  nutri- 
tion a  loss  of  fat  may  hi>  broughl  aboul  without  damage  to  the  muscle;  hut 

great  care  must  he  exercised.     In  the  -i  favorable  cases  tin'  method  can  be 

pursued  only  for  a  period  <>f  a  \'rw  week-,  or  at  mosl  a  few  months,  provided 
all  goes  well.  Further,  this  method  can  only  be  risked  in  obese  patient-  who 
an-  still  in  good  muscular  condition:  for  only  very  strong  constitutions  can 
endure  -iieh  a  diet  for  any  length  of  time.  On  account  of  this  limited  applica- 
tion, the  ••  no-fat  "  cures  do  not  fulfil  the  requirements  which  a  truly  rational 
cure  of  obesity  call-  for.  In  such  a  method,  for  instance,  it  is  desirable  thai 
the  patient  should,  without  danger  to  his  health  and  without  too  great  priva- 
tion, he  able  to  continue  the  diel  permanently  after  the  resull  has  been  <>h- 
tained.  though  perhaps  with  slighl  modifications.  Such  modifications  have, 
however,  noi  been  proposed  by  any  of  the  exponents  of  these  methods  if  we 

except     the    advice    of    Cantani    that,    in    ca-e    his    dietary    regulations    prove 

impracticable,  the  Banting  cure,  i.e.,  the  regime  of  Thomas  K.  Chambei 
to  he  substituted.     I  do  not  believe  that   such  modifications  of  antifal  cures 

are  possible  without  violating  and  completely  overthrowing  their  principle. 
In   -mil  a  modification  the  amount  of  albumin  which  is  to  he  consumed  mu-t 

be  lessened,  and  either  fat  <»r  carbohydrates  substituted   in  a  corresponding 


166  OBESITY 

amount.  Of  course,  under  such  circumstances,  the  diet  loses  its  significance, 
which,  after  all,  consists  in  the  large  amount  of  albumin  which  the  patient 
is  supposed  to  consume. 

The  shortcomings  of  the  "  no-fat "  cures,  especially  the  fact  that  at  best 
they  admit  of  but  temporary  employment,  caused  me  to  propose  in  the  year 
1882  a  method  for  the  treatment  of  obesity  which  is  free  from  the  objection- 
able features  of  those  previously  mentioned,  and  which,  without  losing  its 
distinguishing  characteristics,  may  be  variously  modified  from  time  to  time 
according  to  whatever  conditions  may  arise.  My  method,  which  is  by  no 
means  a  modification  of  the  Banting  cure,  permits  a  manner  of  life  which 
differs  but  little  from  that  of  other  plain  and  sensible  persons.  My  plan  can 
be  continued  indefinitely  by  the  person  in  question  without  the  exercise  of 
too  great  self-denial.  By  this  means  alone  is  it  possible  to  retain  perma- 
nently what  has  once  been  achieved.  The  treatment  of  obesity  is  a  rational 
one  only  when  we  endeavor  to  bring  about  a  lasting  cure,  and  not  only  a  rapid 
transitory  result,  We  can  never  succeed  permanently  with  any  method  of 
treatment  if  the  patient  follows  it  only  for  a  certain  length  of  time  and  then 
returns  to  his  former  mode  of  life;  that  which  has  shown  itself  as  curative 
must  form  a  permanent  and  integral  constituent  of  his  future  manner 
of  life. 

The  conceptions  which  led  me  to  propose  for  obese  persons  a  diet  which 
should  be  curative,  and,  in  its  main  principles,  could  be  maintained  during 
life  were  chiefly  the  following:  It  is  sufficiently  proven  by  experience  that 
even  in  fat  persons  the  ingestion  of  a  measured  quantity  of  fat  under  certain 
circumstances  fails  to  produce  any  accumulation  of  fat,  and  that  the  person 
in  question  may  even  rid  himself  of  his  superfluous  fat  provided  that  the 
carbohydrates  are  properly  limited  and  that  his  manner  of  living  is  otherwise 
normal  and  in  accordance  with  the  fundamental  laws  of  the  modern  phys- 
iology of  nutrition.  I  have,  therefore,  abjured  the  fat-depletion  cures  and 
assigned  to  fat  the  place  which  it  should  occupy  in  the  diet  of  the  obese.  The 
prohibition  of  fat  is  entirely  opposed  to  the  physiological  laws  of  normal  nutri- 
tion. Fat  is  a  necessary  food.  Xo  less  prominent  a  physiologist  than  Don- 
ders  refers  to  this  as  follows :  "  Too  little  fat  undermines  the  organism,  and 
lays  a  foundation  for  faulty  nutrition,  a  poor  admixture  of  the  nutritive  juices 
and  of  the  tissues."  That  this  law  is  not  operative  for  the  obese  can  neither 
be  proven  by  scientific  reasoning  nor  inferred  from  professional  experience. 
Even  Hippocrates  advised  for  the  obese  the  ingestion  of  foods  prepared  with 
fat,  as,  in  this  manner,  the  appetite  was  most  rapidly  satisfied.  This  obser- 
vation of  Hippocrates  is  perfectly  correct. 

It  is,  therefore,  an  ancient  law  of  experience  that  by  the  addition  of  a  cer- 
tain amount  of  fat  to  the  food  the  sensation  of  hunger  is  more  lastingly  re- 
moved than  by  food  very  deficient  in  fat,  or  by  an  equivalent  amount  of  carbo- 
hydrates or  of  albumin.  Fatty  foods  act  in  this  way  not  because  they  spoil 
the  appetite  nor  (as  has  been  maintained  by  some)  because- they  produce  dys- 
peptic symptoms.  On  the  contrary  we  see  that  dyspeptic  symptoms  appear 
frequently  after  the  ingestion  of  too  large  quantities  of  meat.  That  one  may 
eat  enormously  of  meat  without  a  sensation  of  satiety  is  well  known.     Quite 


TREATMENT  167 

similar  are  the  experiences  in  regard  to  carbohydrates.  The  question  why  fat 
satiates  us  most  rapidly  may  be  very  easily  explained  by  the  observations  of 
M.  .Matthes  and  E.  Marquardsen  (Verhandl.  d.  Congr.  für  innere  .1/"/..  1S98, 
XV!,  p.  358  u.  flg.).  These  observers  have  shown  that  fats  remain  in  the 
stomach  for  a  long  time,  and  that  large  amounts  of  fat  necessitate  a  very 
large  expenditure  of  the  regulatory  powers  of  the  stomach,  and  produce  a 
decided  encumbrance  of  the  same.  As  in  my  diel  regulations  too  great 
amounts  of  fat  are  not  permitted  the  obese,  the  deleterious  effects  arising  there- 
from are  not  to  be  feared.  Further,  the  inclusion  of  fat  is  by  no  means  a 
cure  by  means  of  nausea,  as  has  been  stated  by  one  author.  It  is  in  fad  not 
a  cure  but  a  mode  of  living  whereby  fat  simply  assumes  its  proper  function 
as  a  food. 

To  attain  this  purpose,  no  larger  amount  of  tat  is  necessary  than  is  per- 
mitted to  non-obese  persons,  even  to  those  who  are  subjected  to  the  hardest 
labor.  ///  the  nutrition  of  the  obese  the  limitation  in  the  amount  of  carbo- 
hydrates is  the  chief  point.  Of  course,  this  does  not  mean  that  an  intolerable 
limitation  of  vegetable  food  is  necessary.  On  the  contrary,  in  the  nutrition 
of  f';it  persons  a  plentiful  use  is  to  be  made  of  green  vegetables  rich  in  water 
and  poor  in  carbohydrates,  since  their  pre-eminent  qualifications  as  satiating 
foods  and  fat  carriers  make  them  especially  suitable.  Only  vegetables  rich 
in  starch,  such  as  turnips,  potatoes,  etc.,  are  to  be  avoided.  By  this  method 
fat  is  administered  to  the  patient  in  such  wise  as  to  cause  no  repugnance,  and 
the  carbohydrates  may  be  limited  by  giving  a  bread  richer  in  albumin  than  is 
osually  taken — a  point  to  which  I  called  attention  a  number  of  years  ;i.r". 
Our  ordinary  bread  contain-  only  about  6  to  7  per  cent,  of  albumin,  and  it- 
nutritive  product  i<  almost  exclusively  -larch.  The  starch  may  be  decidedly 
reduced  if  the  albumin  content-  of  the  bread  are  increased  by  the  addition 
of  vegetable  albumin.  In  this  manner  it  is  easy  to  prepare,  even  at  home, 
a  very  palatable  bread  which  will  contain  from  20  to  •">n  per  cent,  of  albumin. 

I    have   repeatedly  published   the    formulas   necessary    for  this   purpose,   la-t    in 

the  article  by  Schwalbe  and  myself  on  Diabetes  Mellitus  in  the  •■  Handbuch 
der  praktischen   Medicin,"  Stuttgart.  1901.     For  the  preparation  of  such  a 

bread  we  require  pure  vegetable  albumin,  which  may  be  obtained  from  a  num- 
ber of  plant-.  Vegetable  albumin  i-  easily  digested,  readily  utilized  by  the 
human  organism,  and  is  not  only  very  much  cheaper  than  meat   but.  for  many 

other  reasons,  i-  even  preferable.  I'p  to  very  recent  times  but  two  such  pure 
vegetable  albumin-  were  ;it  ..Hi'  disposal,  one  of  which  was  discovered  by  Dr. 
Johannes  Elundhausen  of  Hamm  i.  \V..  and  manufactured  from  gluten,  a 
patent  albumin  which  the  inventor  «all-  "  aleun.nat ."  In  addition  to  -mall 
quantities  of  salts  (0.78  per  cent.)  and  cellulose  (0.45  per  cent.)  aleuronai 
contains  at  least  so  per  cent,  of  albumin,  about  ;  pei-  cent,  of  carbohydrates, 
and  about  !»  per  cent,  of  water.  The  second  vegetable  albumin,  placed  at  our 
disposal  later  than  aleuronat,  is  the  rice  albumin  "ergon"  which  i<  manu- 
factured by  Dr.  Hen-el  &  Co..  in  the  chemical  laboratory  at  Lesum  near 
Bremen. 

This  is  not  the  place  at  which  to  enumerate  the  varied  uses  we  may  make 

of  vegetable  albumin   in   the  nutrition  of  patient-  with  diabetes  mellitus.      In 


168  OBESITY 

obesity  as  well  as  in  gout  we  utilize  vegetable  albumin  almost  exclusively  for 
the  preparation  of  a  bread  rich  in  albumin,  by  which  we  may  satisfy  a  greater 
albumin  requirement  in  the  individual  than  is  possible  by  means  of  our  ordi- 
nary bread.  In  this  manner  larger  amounts  of  bread  may  be  permitted  than 
would  otherwise  be  allowable,  which  is  very  acceptable  to  the  patient.  By 
the  aid  of  these  vegetable  albumins  we  may  produce  a  bread  which  is  entirely 
unobjectionable ;  frequently,  however,  such  a  bread  is  distasteful.  This  is  due 
to  the  fact  that  the  necessary  care  has  not  been  observed  in  its  preparation.  It 
therefore  appears  to  me  worth  while  to  give  some  directions  and  a  few  recipes 
for  the  preparation  of  these  breads  rich  in  albumin,  such  breads  as  are  useful 
in  the  dietetic  treatment  of  obesity  and  gout.  To  ensure  a  faultless  bread, 
absolutely  necessary  prerequisites  are:  1.  Scrupulous  cleanliness  of  all  uten- 
sils and  purity  of  all  ingredients;  2.  A  pure,  starch-free,  compressed  yeast 
(common,  so-called  baker's  yeast  may  be  adulterated  with  starch  flour  up  to 
50  per  cent.)  with  good  fermenting  power — for  the  preparation  of  good  aleu- 
ronat  or  ergon  bread  requires  a  larger  quantity  of  yeast  than  other  breads; 
3.  An  exact  following  of  the  recipes  in  regard  to  the  amount  of  fluid. 


1.   RECIPE   FOR   THE   PREPARATION  OF  WHEAT   BREAD  WHICH  CONTAINS 
A.BOUT   27.5   PER  CENT.   OF  ALBUMIN 

(Before  the  addition  of  any  liquids.) 

600  grams  of  wheat  flour, 
150  grams  of  aleuronat  or  ergon, 
10  grams  of  yeast, 
\  liter  of  milk, 
5+  grams  of  common  salt, 
About  one  gram  of  sugar  (i.  e.,  as  much  as 
the  yeast  requires  for  fermentation). 


Proportion  of  aleuronat  or  ergon  to  wheat 
flour  as  1 : 4. 


The  flour  and  aleuronat  are  to  be  well  mixed  in  a  pan  previously  warmed  to  about 
30°  C.  A  small  portion  of  the  milk  is  warmed  to  about  the  same  temperature,  and 
after  one  gram  of  sugar  has  been  dissolved  in  it  the  mixture  is  poured  upon  the  crumbled 
yeast,  and  the  whole  set  in  a  warm  place  at  not  over  30°  O,  and  allowed  to  stand  until 
it  ferments.  This  mixture  is  then  poured  into  the  center  of  the  flour  and  aleuronat 
( or  ergon )  mixture  in  such  a  way  that  the  outer  borders  of  the  flour  are  not  moistened. 
Next  the  remainder  of  the  warm  (30°  C.)  milk  and  the  salt  are  stirred  in  with  a  spoon, 
still  keeping  the  outer  portions  of  the  dough  dry.  The  vessel  must  then  stand  in  a 
warm  place  (30°  C. )  covered  with  a  cloth  until  the  dough  rises;  then  it  is  to  be  mixed, 
first  with  a  spoon  and  then  lightly  with  the  hands  (firm  kneading  is  to  be  avoided), 
with  the  dry  flour  still  remaining  at  the  edges  until  a  soft  dough  is  formed  from  the 
entire  mass.  It  is  then  made  into  small  loaves  which  are  allowed  to  rise  in  a  baking 
pan  slightly  warmed  (30°  C. ),  greased  with  butter.  After  they  have  risen,  the  loaves 
are  glossed  over  with  melted  butter  and  baked  for  one-half  or  three-quarters  of  an  hour. 
Brushing  the  surface  of  the  loaves  with  cold  water  before  they  are  taken  from  the 
oven  gives  them  greater  luster.  These  loaves  may  be  eaten  on  the  day  of  baking,  or 
even  a  day  or  two  later,  but  are  better  if  placed  in  the  oven  and  re-baked.  Bread 
containing  fat,  and  very  palatable,  may  be  made  by  adding  butter  to  the  mixture  of 
warm  milk  and  table  salt  in  a  proportion  of  about  50  grams  of  butter  to  about  one  pound 
of  dough.     This  bread  also  is  to  be  smeared  with  butter,  and  baked  in  a  pan. 


TREATMENT  169 


2.  RECIPE    FOR    THE    PREPARATION    OF    RYE    BREAD    WHICH    CONTAINS 
ABOUT  27.5  PER  CENT.   OF   ALBUMIN 

(Before  the  addition  of  liquids.) 

1,200  grams  of  rye  flour, 
300  grains  of  aleuronat, 
30  grams  of  sour  dough,1 
About  12  grams  of  table  salt, 
About    1.5   liters  of   lukewarm   water,  and 
lastly,  some  caraway  seed  (if  desired). 


Proportion  of  aleuronat  to  rye  flour  as  1 : 4. 


On  the  evening  before  baking,  flour  and  aleuronat  (or  ergon)  haying  been  previously 
warmed  are  thoroughly  mixed  in  a  vessel  warmed  to  30°  C.  To  this  mixed  (lour  add 
the  sour  dough  winch  has  been  previously  mixed  with  some  of  the  lukewarm  water,  and 
is  now  poured  into  a  hollow  in  the  center  of  the  mass  of  Hour,  the  outer  borders  of  the 
flour  remaining  dry  ami  untouched.  Now  the  dry  aleuronat  (or  ergon)  mixture  at 
the  edges  is  mixed  with  the  watery  mixture  of  sour  dough  in  the  center  while  we 
gradually  add  the  resl  of  the  water,  stirring  from  the  center  tu  the  periphery.  After 
thia  is  done,  the  entire  mass  in  the  vessel  is  sprinkled  with  the  aleuronat  (ergon) 
Hour  mixture,  and  the  dough  prepared  in  this  manner  i-  allowed  to  stand  over  night 
(about  twelve  hours),  well  covered  and  kept  warm  at  about  ■'JO0  C.  In  the  morning 
salt  and  caraway  -eed  are  added,  and  the  ma--  i-  kneaded  at  once.  If  the  dougb  i-  too 
-till'  it  may  he  made  more  spongy  by  the  addition  of  lukewarm  water,  and  if  it  is  too 
sticky  Hour  and  aleuronat  (or  ergon),  1  to  1,  may  be  kneaded  in.  Then  the  dough 
is  placed  in  a  -hallow  iron  pan,  covered  with  a  linen  cloth,  and  Bet  in  a  warm  place  at 
about  30  C.  f<>r  2  to  2|  hours,  ti>  rise.  When  light  the  loaves  are  brushed  with  melted 
butter,  and  baked  for  aboul  1  to  2\  hours.  To  test  whether  the  I. read  i-  dune,  a  splinter 
of  wood  may  lie  introduced  into  a  loaf,  and  if.  on  withdrawing  it.  no  nmi-t  dough 
adhere-  to  it  the  bread  is  thoroughly  baked.  It  is  advisable  during  the  last  »pari  of  the 
baking  to  turn  the  loaves  in  the  pan.  This  bread  should  not  lie  cut  until  the  next  day. 
It  -hould  he  kept  in  a  cool  place,  and  in  the  summer  in  the  refrigerator. 

of  course,  bread  containing  less  aleuronat  or  ergon  may  he  made  cither  with  wheat 
Hour,  or  with  rye  dour.  Thus,  for  example,  we  can  make  bread  which  contain-  one  and 
a  half  time-  a-  much  or  double  the  amount  of  albumin  (in  dry  substance)  contained 
in  ordinary  bread,  which,  a-  i-  well  known,  contains  aboul  ten  per  cent,  of  albumin 
(dry).  To  make  bread  containing  aboul  fifteen  per  cent,  of  albumin  in  the  dried 
condition,  add  one  pari  of  aleuronat  or  ergon  to  aboul  twentj  parts  of  Hour:  to  make 
bread  containing  aboul  twenty  per  cent,  of  albumin  (dry),  add  aboul  one  pari  of 
aleuronat  or  ergon  to  eighl  parts  of  Hour.  The  -mallei-  the  amount  of  aleuronat  or  ergon 
the  easier  it  i-  to  make  aleuronat  or  ergon  bread.  It  i-  therefore  advisable  for  an 
amateur  in  bread  baking  to  begin  with  «me  of  the  weaker  aleuronat  or  ergon  breads 
according  to  the  recipes  ju-t  given.    The  breads  containing  larger  quantities  of  albumin 

can   then    he   made   with   greater  certainty    and    ease. 

Recently  the  Dumber  of  vegetable-albumin  preparations  h:\-  greatly  in- 
creased. Among  these  may  be  mentioned  the  producl  of  Niemöller  in 
Gütersloh  i.  \V.  from  grain,  und  called  " roborat."  For  baking  purposes  thia 
i-  exceedingly  useful.  Further  experiences  will  have  to  Im-  gathered  in  regard 
to  these  preparations,  whose  cumber  will  probably  increase  still   further. 

A  formidable  rival  to  these  vegetable-albumin  preparations  is  fresh  casein. 
The  investigations  undertaken  in  my  clinic  by  E.  Schreiber  (Centralbl.  f. 
8toffwechsel-  und  Verdauungskrankheiten,  1901,  Nr.  .". )  have  shown  thai  there 

i1  Rye  Hour  dough  from  a  previous  baking,  which  ha-  been  Bel  aside  for  several  days, 

and    ha-    t  ill  lied    -our.       |  .1.    I..   S.J  ) 


170  OBESITY 

is  no  cheaper,  and  at  the  same  time  more  palatable,  albumin  for  these  pur- 
poses. Bread  produced  from  fresh  casein  (casein  bread)  may  of  course  be 
also  utilized  in  the  nutrition  of  gouty  patients,  for  casein  does  not  produce  an 
increase  in  uric  acid  excretion.  The  bread  made  with  this  casein  can  be 
readily  baked  by  any  baker.  I  have  often  used  it  with  advantage  in  the 
nutrition  of  the  obese,  of  gouty  patients,  and  particularly  also  in  diabetes 
mellitus. 

It  is  obvious  that  within  certain  limits  leguminous  vegetables  may  also 
be  utilized  in  the  nutrition  of  the  obese.  Besides  a  plentiful  amount  of  albu- 
min these  vegetables  contain  much  carbohydrate,  but  with  a  corresponding 
limitation  of  the  other  carbohydrates  of  the  diet,  they  may  be  used  with  advan- 
tage. The  discreet  use  of  fruit  not  too  sweet,  and  of  stewed  fruit  without 
the  addition  of  sugar,  is  permitted.  Sugar,  puddings,  and  starchy  foods  of 
other  kinds,  as  well  as  potatoes  and  all  dishes  made  from  them,  are  absolutely 
prohibited  for  the  obese.  A  small  quantity  of  wine  deficient  in  sugar  and 
containing  small  amounts  of  alcohol  may  be  given,  provided  the  patient  can- 
not get  along  without  it.  Beer  I  prohibit.  This  is  generally  one  of  the  most 
severe  trials  which  the  obese  patient  is  called  upon  to  undergo.  Brillat-Savarin 
is,  however,  quite  correct  when  he  says  to  the  obese :  "  Avoid  beer  as  you 
would  the  pest."  But  with  regard  to  tobacco,  provided  there  is  no  contra- 
indication on  account  of  the  heart,  I  permit  a  moderate  indulgence — two  or 
three  mild  cigars  a  day. 

Finally,  regarding  the  proper  quantity  of  albumin  for  corpulent  individ- 
uals, of  course  all  superfluous  proteid  must  be  reduced  according  to  the  indi- 
vidual requirements,  as  in  the  antifat  methods  of  treatment.  Certainly  custom 
permits  entirely  too  much  latitude  in  this  direction,  and  often  the  patients 
take  far  too  much  albumin.  We  have  seen  that  by  including  vegetable  albu- 
min in  the  diet,  a  considerable  amount  of  the  albumin  needed  by  the  body 
is  provided.  On  the  other  hand.  I  must  emphasize  that,  in  such  a  diet,  the 
patients  have  all  the  variety  necessary  for  those  who  live  under  normal  condi- 
tions, and  who  do  not  perform  excessive  bodily  labor.  With  this  diet,  wherein 
the  fatty  foods  fill  their  proper  place,  we  find  that  hunger  is  more  easily  satis- 
fied than  with  an  antifat  diet,  and  that  the  thirst  which  occurs  in  all  antifat 
cures  is  also  avoided.  If  thirst  were  not  a  constant  feature  in  "  antifat  cures  " 
it  would  be  unnecessary  to  make  such  statements  as  that  the  patients  "  must 
learn  to  endure  thirst."  The  effect  of  fat  in  diminishing  thirst  has  been 
observed  and  dwelt  upon  by  so  many  competent  authorities  that  it  is  unneces- 
sary for  me  to  enter  more  minutely  into  this  subject.  If  the  method  of  treat- 
ment proposed  by  me,  or,  let  us  say,  the  "  proper  manner  of  life  for  the  obese/' 
is  maintained  (controlled,  of  course,  by  an  expert),  eventually  the  superfluous 
fat,  and  only  this,  will  gradually  disappear.  A  too  rapid  loss  of  weight  is 
injurious.  Loss  of  fat  should  always  occur  slowly,  and  must  be  brought  about 
with  great  care.  The  method  must  never  be  allowed  to  fall  into  a  rigid 
routine,  but  must  be  arranged  according  to  the  individual  conditions  of  each 
case;  and  it  must  also  be  so  arranged  that  the  patient  may  pursue  his  ordinary 
occupation  without  detriment. 

A  few  examples  will  serve  to  illustrate  briefly  the  manner  of  life  advised 


TREATMENT  171 

by  me.  Xo  hard  and  fast  rules  can  be  given  because,  as  I  have  several  times 
stated,  the  method  should  never  become  a  routine  affair.  For  example,  in 
the  first  case  (see  below)  if  instead  of  the  ordinary  rye  and  wheat  bread,  a 
bread  richer  in  albumin  is  chosen,  the  ration  of  bread  must  naturally  bo  in- 
creased and  the  daily  quantity  of  meat  correspondingly  diminished,  etc.  Three 
meals  a  day  I  believe  to  be  the  best  rule.  Yet  even  here  some  modification 
might  become  necessary.  In  spite  of  many  slight,  but  important,  variations 
the  general  principles  remain  the  same. 

Observation  I. — A  man,  forty-four  years  of  age,  moderately  muscular,  suffered  from 
increasing  corpulence  though  he  was  otherwise  healthy  and  had  formerly  been  thin. 
He  led  an  active  life,  but  limited  his  exercise  to  that  in  the  house.  He  was  of  very 
temperate  habits,  especially  in  the  use  of  alcohol.  The  obesity  had  evidently  developed 
as  the  result  of  a  very  profuse  ingestion  of  albuminous  food,  with  the  careful  avoidance 
of  fat,  but  with  a  fondness  for  carbohydrates,  particularly  for  sweets.  The  diet  which 
I  had  the  patient  follow  was  about  as  follows: 

1.  Breakfast  (in  summer  at  six  or  half-past  six  o'clock)  :  A  large  cup — about  250  cc. 
— of  strong  tea  without  milk  or  sugar;  50  grams  of  bread  (wheat  or  rye  bread),  toasted, 
with  20  or  30  grams  of  butter. 

2.  Midday  /n<<il  (between  two  and  half-past  two  o'clock»:  Meat  broth,  frequently 
with  hone  marrow  in  a  solid  form  (the  bone  should  hi'  cooked  for  an  hour  to  an  hour 
and  a  half  so  that  the  marrow  docs  not  melt  )  or  with  an  egg,  or  other  suitable  addition; 
120  to  180  grams  of  boiled  or  broiled  meat,  preferably  fat  meat  if  it  agrees  with  him; 
vegetables  as  mentioned  above,  preferably  peas,  lentils  or  beans.  For  dessert,  some 
fresh  fruit  if  obtainable,  particularly  strawberries,  cherries,  and.  best  of  all.  apples. 
A  salad,  according  to  the  season:  also  apple-sauce  freshly  cooked  or,  if  unobtainable, 
stewed  dried  or  preserved  fruit,  always,  however,  without  sugar. 

As  fluid:  Two  to  three  glasses  of  a  light  Rhine  wine. 

Soon  after  this  meal   a    large  cup    (about    2.~>0  cc. )    of  strong  tea   without   sugar. 
."{.  Supper  (between  seven  and  a  half  and  eight  o'clock)  :  In  winter  almost  invariably, 
in   summer   occasionally,   a    cup    Of   tea    as    in    the    morning    and    after    the   midday    meal; 

an  egg  or  roast  meat,  preferably  fat.  or  some  ham  with  fat.  or  Cervelat  Bausage,  or  fish, 
smoked  or  fresh;  a  total  of  7">  to  so  grams  of  meat,  aboul  30  grams  of  wheat  bread, 
and  I.")  to  20  grams  of  fat.  this  depending  on  the  amount  of  fat  in  the  meat,  with  more 
or  less  butter.  Occasionally  a  small  quantity  of  cheese  and  aome  fic-li  fruit  or  Btewed 
dried  fruit. 

This  diet  was  combined  with  moderate  exercise  in  the  open  air:  on  Sundays  he  took 
walks  usually  lasting  several  hours,  and  these  were  continued  during  the  summer  holi- 
days when  a  residence  "i  several  weeks  at  the  seashore  or  in  the  Alps  interrupted  his 
ordinary  work.  The  effect  on  the  patient's  bodily  health  and  mental  activity  was  very 
good.  The  diet  agreed  excellently.  A  second  breakfast  was  never  taken,  hut  he  was 
always  hungry  for  the  midday  meal.  There  was  a  remarkable  decrease  in  the  previously 
extreme  i hirst,  in  the  evening  the  craving  for  food  was  not  very  great,  and  was  easily 
satisfied.  In  the  course  of  Bis  months  he  lost  22  pounds,  gradually  hut  Bteadily,  a-  i- 
desirable  in  all  Buch  cases,  and  in  aboul  nine  months  his  waisl  measurement  decreased 
16  cm.  This  diet,  in  the  main,  has  been  continued.  As  time  passed  the  ingestion  of 
fluid  was  still  further  decreased.  Instead  of  a  large  cup  of  tea  three  time-  daily, 
he  now  took  a  small  cup  only  in  the  morning,  and  in  the  evening  coffee,  which  formerly 
had  not  been  well  borne;  the  daily  use  of  wine  hid  been  stopped  tor  years.  Only  at  the 
beginning  of  the  regulation  of  the  diet  was  it  necessary  to  weigh  the  allowance  of 
the  individual  foods,  lie  Boon  learned  to  estimate  them  verj  readily.  After  the  use 
of  aleuronat  became  known,  it  was  employed  bj  this  patient  verj   largely. 

Observation    [I.     While  in  the  first   observation  we  were  dealing  with  a   i  i 
uncomplicated  obesity,  this  one  concerns  a  lady  who  Buffered   from  obesity  complicated 
by  gout.    The  patient  is  thirty  seven  years  of  .\^r.  the  wife  of  an  officer  from  k.     The 
patient  had  do  Bpecial  family  predisposition  to  obesitj   or  gout.     In  her  youth  -he  was 


172  OBESITY 

painfully  thin,  and  began  to  menstruate  at  eleven  years  of  age.  She  was  apparently 
anemic,  but  otherwise  strong  and  without  any  symptoms  of  importance.  She  married 
at  nineteen,  aborted  after  eight  weeks,  and  within  a  few  months  became  stout  and 
remained  so  for  almost  nine  months.  During  this  time  her  husband  died.  As  a 
widow  she  again  became  as  thin  as  when  she  was  a  girl  and  remained  so  during 
her  widowhood  (seven  years),  during  which  time  she  was  occasionally  very  ane- 
mic. After  her  second  marriage,  the  patient  soon  became  pregnant.  After  the  birth 
of  a  girl  (autumn,  1890)  the  patient  became  very  stout,  again  lost  some  flesh  in 
the  next  few  years,  but  in  1893,  after  a  serious  miscarriage,  she  again  became  very 
stout  and  under  the  influence  of  an  injudicious  mode  of  life  she  remained  so  up  to  March, 

1898,  when  she  consulted  me  for  the  first  time.  After  this  miscarriage  an  exudate 
formed  in  the  pelvis,  and  she  has  since  then  suffered  from  obstinate  constipation  :  it  was 
on  this  account  that  she  desired  treatment.  Besides  this,  the  patient  suffered  from 
gout  which  had  appeared  for  the  first  time  in  1886,  and  was  localized  in  the  fingers, 
being  diagnosticated  by  Professor  Lücke  in  Strassburg.  On  this  account  Professor 
Lücke  ordered  a  course  of  Vichy  water  at  the  Springs.  At  this  time  a  diJieulty  in 
hearing  appeared  for  the  first  time  and  gradually  increased.  In  January,  1898,  an 
acute  attack  of  gout  occurred  in  the  great  toe  of  the  right  foot,  and  lasted  eight  days. 
For  some  years  cramps  had  occurred  in  the  calves  and  feet,  mostly  at  night  when  the 
patient  went  to  bed,  but  also  during  the  night,  and  they  recurred  almost  every  night, 
especially  in  the  right  leg.  Early  in  March,  1S98,  severe  pains  were  suddenly  felt  in 
the  great  toe  of  the  right  foot.  The  toe  swelled  somewhat  and  became  red.  In  about 
ten  days,  during  which  period  the  patient  was  unable  to  stand  upon  the  foot  for  several 
days,  the  attack  subsided.  From  the  14th  to  the  25th  of  April,  1898,  the  patient  suffered 
from  an  attack  of  influenza,  during  the  course  of  which  the  temperature  rose  to  102.2°  F., 
and  she  was  much  debilitated.  About  the  9th  of  May  of  the  same  year,  suddenly  and 
during  her  menstrual  period,  an  attack  of  gout  supervened.  This  was  localized  in  the 
little  finger  of  the  left  hand,  and  ran  a  typical  course  in  a  very  short  time.  LTpon  the 
12th  of  the  same  month,  the  redness  of  the  affected  area  had  disappeared.  At  the  begin- 
ning of  June  the  patient  complained  of  decided  gouty  pains  in  the  feet.  The  first 
metatarsophalangeal  joints  of  both  feet  were  very  sensitive  to  pressure.  No  typical 
attack  developed,  however,  When  the  patient  stopped  treatment  upon  the  23d  of  June, 
she  was  able  to  walk  quite  a  distance  without  difficulty. 

In  this  case  the  treatment  was  first  directed  against  the  obesity,  gout,  and  also 
particularly  the  stubborn  constipation.  For  evacuation  of  the  bowels,  large  enemata 
of  oil  were  used  with  good  effect.  A  diet  was  instituted  according  to  the  principles 
laid  down  by  me,  and,  in  so  far  as  gout  permitted,  walking  was  ordered  for  active  bodily 
exercise,  which  was  supplemented  by  massage  of  the  body.  As  a  drug,  the  prolonged 
use  of  0.5  (7£  grains)  urotropin  in  a  quarter  of  a  liter  of  alkaline  water  to  be  taken 
twice  daily  was  prescribed.  Her  weight  fell  during  this  time  from  199  pounds  to  187 
pounds.  This  success  was  evidently  not  due  to  the  diet  alone,  which  under  the  circum- 
stances could  not  be  strictly  carried  out.  During  this  time  a  severe  influenza  occurred 
from  which  the  patient  slowly  recovered,  also  quite  severe  gout  which  of  course  also 
decreased  the  body-weight.  When  I  saw  the  patient  again  in  October  of  the  same  year, 
the  constipation  had  been  relieved  by  the  continuance  of  the  enemata,  the  gouty  diffi- 
culties had  not  recurred,  but  there  was  a  decided  psychical  depression  which  was 
increased  by  various  external  conditions.  The  weight  had  again  risen  to  194.5  pounds, 
and  the  patient  had  resumed  her  former  manner  of  living,  which  was  conducive  to  the 
accumulation  of  fat.  The  weight,  when  she  decided  to  renew  her  treatment,  had  risen 
to  203   pounds.     Treatment   began   at   my   private   hospital   upon    the    28th   of   August, 

1899,  and  ended  upon  the  5th  of  December,  1899.  This  time  the  treatment  was  not 
hindered  by  disturbing  intermediate  maladies  such  as  the  attack  of  influenza  and  the 
two  attacks  of  gout  during  the  first  period  of  treatment.  The  function  of  the  intestine 
had  been  greatly  improved.  Of  course,  it  was  decidedly  retarded  by  a  very  pendulous 
abdomen.  The  gouty  pains  had  by  no  means  completely  disappeared.  The  use  of 
urotropin  was  continued,  besides  the  diet  which  was  regulated  according  to  my  princi- 
ples.   The  weight  of  the  patient  was  as  follows :  Weight  upon  the  28th  of  August,  203.86 


TREATMENT  173 

pounds;  upon  the  2d  of  September  as  well  as  upon  the  9th  of  September,  203  pounds; 
upon  the  15th  of  September  as  well  as  upon  the  23d  of  September,  200  pounds:  upon 
the  30th  of  September,  198  pounds;  upon  the  7th  of  October.  196  pounds  i  health  decidedly 
improved,  can  walk  well);  upon  the  14th  of  October,  193  pounds;  upon  the  21s<  of 
October,  19:}  pounds;  upon  the  28th  of  October.  191  pounds:  November  3d,  190  pounds; 
upon  November  11th.  189  pounds;  upon  November  18th,  1st  pounds;  upon  November  25th, 
ISO  pounds:  upon  the  4th  of  December,  185.51  pound-.  The  total  decrease  in  weight 
amounted  to  is.:;.")  pounds.  The  patient  lost  weight  slowly  and  steadily,  about  one 
pound  a  week.  At  the  same  time  the  general  condition  and  bodily  activity  had  greatly 
improved.  The  psychical  depression  had  disappeared  except  for  a  few  slight  rdap-es. 
The  gouty  difficulties  were  present  to  only  a  slight  extent,  if  at  all.  Later  reports 
regarding  the  health  of  this  patient  have  been  very  favorable. 

A  more  or  less  slow  result  which  in  the  end  may  perhaps  prove  fairly  sat- 
isfactory occurs  in  those  cases  in  which  the  patients  do  not  exactly  follow  the 
regulations,  hut  make  changes  of  their  own  accord.  I  shall  mention  only  one 
case  of  this  kind.  A  high  government  official  (lawyer),  forty-five  years  old, 
weighing  22]  pounds;  circumference  of  the  abdomen  at  the  height  of  the 
navel  123  cm.  lie  believed  that  he  could  not  get  along  without  beer  and  a 
larger  amount  of  bread — and  so  increased  this  to  160  grams  of  rye  bread — 
and  took  one  liter  of  beer  daily.  In  the  main  he  followed  directions,  and  to 
compensate  for  his  deviation  he  walked  ^\^vy  afternoon  for  an  hour  and  a 
half.  In  the  firsl  six  months  he  lost  31  pounds,  in  the  second  six  months  i;i 
pounds,  in  the  third  six  months  2.2  pounds,  a  total  of  39^  pounds.  The  cir- 
cumference of  the  abdomen  diminished  34  cm.  Entirely  satisfied  with  these 
results,  the  patient  continued  to  live  according  to  the  principle-  under  which 
he  bail  gotten  rid  of  his  numerous  difficulties. 

Any  one  desirous  of  success  with  this  method  must  have  a  certain  knowl- 
edge of  the  modern  physiology  of  nutrition,  and  mu-t  recognize  the  necessity 
of  changes  to  meet  the  pathologic  condition-  peculiar  to  each  individual  and 
his  general  circumstances. 

These  are  essentially  the  rule-  according  to  which  an  obese  person  must 
arrange  his  diet  if  he  desires  to  rid  himself  of  superfluous  fat  and  prevent  its 
reaccumulation.  To  carry  out  this  regime  doe-  not  give  rise  to  difficulties; 
the  privations  which  are  caused  by  it  areas  nothing  in  comparison  with  those 
which  are  caused  by  obesity  and  with  the  dangers  which  may  in  this  way  be 
avoided.  It  is  presupposed  that  while  carrying  oul  these  dietetic  rule-  a 
suitable  amount  of  exercise  mu-t   be  taken.     One  of  the  advantages  of  my 

method  of  treatment    is  that    the  patients  may   follow   their  u-ual  occupations, 

and  that  thus  the  ordinary  movements  of  the  body  may  be  made  serviceable  in 
the  treatment.     Especially  exhausting   muscular  movements  are   inadvisable 

for  persons  who  are  both  fat  and  anemic,  since  tiny  give  ri-e  to  certain  diffi- 
culties,  are   almost    always    impossible   to  carry   out,    and    are  by   no    mean-    bo 

successful  in  reducing  tat  as  they  are  often  claimed  to  be.  Banting  in  his 
letters  upon  corpulence  relate-  \ery  entertainingly  how  an  excellent  physician 
well  known  to  him  had  advised,  to  prevenl  the  increase  of  his  corpulence,  thai 
before  beginning  his  u-ual  daily  work  be  should  take  extra  exercise.  As  the 
physician  considered  rowing  very  good  for  this  purpose,  Banting  rowed  a  few 
hour,  early  in  the  morning.     Be  relates  thai  by  ibis  means  he  gained  muscular 


174 


OBESITY 


power — but  simultaneously  a  voracious  appetite,  and  adds  ingenuously  "  As  I 
yielded  to  this,  I  constantly  increased  in  weight  until  my  dear  old  friend  (the 
previously  mentioned  physician)  advised  me  to  give  up  this  kind  of  exercise." 
What  I  have  previously  advised  in  regard  to  exercise  for  the  obese  patient 
(Observation  I)  may  in  general  be  looked  upon  as  sufficient, 

Quite  a  number  of  other  diet  rules  have  been  proposed  by  various 
authors  according  to  the  methods  advised  by  me  in  the  nutrition  of  the  obese. 
Of  course,  I  cannot  and  will  not  enumerate  all  of  these,  for  in  the  treatment 
of  obesity  the  most  varied  diet  schemes  may  be  based  upon  the  foundation 
given.  But  I  shall  mention  the  regime  proposed  by  Hirschfeld,  which  is 
elucidated  by  two  illustrations.  As  is  evident  from  these,  Hirschfeld  requires 
a  "  uniform  "  limitation  of  all  kinds  of  food,  and  maintains  that  the  appetite 
can  be  satisfied  without  any  excess  of  food. 


Example  I. 

Breakfast :  Coffee,  without  cream  or  sugar ; 

1  roll  (50  grams). 
2d  Breakfast :  2  eggs. 
Dinner:  Bouillon   with  about   30  grains  of 

rice  weighed  raw ;    250  grams  of   lean 

meat,   weighed    raw,   either    boiled    or 

broiled  with  a  little  fat, 
Afternoon  :  Coffee,  without  cream  or  sugar. 
Supper :  50  grams  of  cream  cheese ;  100  grains 

of  bread  ;  10  grains  of  melted  fat  (goose 

fat). 


Example  II. 
Breakfast :  As  in  Example  I. 

2d  Breakfast :  Bouillon  and  2  eggs. 
Dinner:  Potato   soup,  300   grams  of   meat, 
weighed  raw. 


Supper :  200  grams  of  lean  ham,  100  grams 
of  bread. 


There  is  contained 


In  diet  No.  1. 
In  diet  No.  2. 


Albumin. 

Fat. 

95  grams 
134       " 

43  grams 
46       " 

Carbohydrates. 
106  grains  =  1,224  calories 
122      "        =  1,478       " 


In  women  it  will  be  possible  to  get  along  with  even  less  food. 

Incidentally,  in  speaking  of  "no-fat"  cures,  I  mentioned  that  they  (in 
contrast  to  my  method  of  treatment)  necessitate  that  the  patient  learn  to  endure 
his  thirst.  The  withdrawal  of  water  played  a  role  in  antifat  cures  even  in 
antiquity.  Pliny  the  Younger  advised  those  who  desired  to  become  thin  to 
refrain  from  fluids  while  eating,  and  even  afterward  to  drink  but  little.  This 
is  not  the  place  in  which  to  follow  in  detail  the  history  of  these  thirst  cures. 
l{  may  be  only  mentioned  here  that  the  father  of  the  latest  movement  in  this 
direction,  which  originated  in  Munich  and  for  a  time  gave  rise  to  much  dis- 
cussion, was  the  founder  of  the  Naturheilansstalt  Brunnthal,  near  Munich, 
Dr.  J.  Steinbacher  (died  1868).  In  his  booklet,  "Asthma,  Fatty  Heart, 
Corpulence,  etc.,"  he  has  laid  special  stress  on  ridding  the  body  of  a  part 
of  its  fluid  in  the  cure  of  obesity.  Oertel,  following  him,. has  developed  this 
method  in  great  detail,  and  it  has  been  named  after  him  the  "  Oertel  Cure." 
The  withdrawal  of  fluid,  upon  which  the  greatest  stress  is  laid,  in  this  method 
may  be  attained  in  various  ways.  First,  by  the  limitation  of  the  fluid  intake. 
This  is  hard.  Thirst  is  much  more  difficult  to  endure  than  hunger.  Most 
persons  very  soon  become  nervous  under  it,  and  will  not  listen  to  reason.     Sec- 


TREATMENT  175 

ondly,  much  fluid  may  be  withdrawn  from  the  body  by  inducing  sweating.  In 
regard  to  this  I  need  only  mention  the  sun  baths  advised  by  Celsus  for  the 
obese.  These  depletion  cures  cause  a  loss  of  body  albumin.  Some  of  the 
reports  of  the  so-called  Oertcl  cure  may  be  given  here.  Oertel  permits  the 
obese  156  to  170  grams  of  albumin,  75  to  120  grams  of  carbohydrates,  25  to 
45  grams  of  fat.  The  upper  limit  Oertel  allows  only  for  those  persons  in 
whom  the  craving  for  food  is  great  owing  to  hard  muscular  work,  for  example, 
mountain-climbing.  On  account  of  the  importance  which  Oertel  attaches  to 
the  ingestion  of  fluid,  he  has  fixed  the  amount  at  973  to  1,414  grams. 

A  sample  diet  list  given  by  Oertel  is  as  follows:  Breakfast:  fine  wheat  bread  35 
grams,  coffee  120  grams,  milk  30  grams,  2  soft-boiled  eggs  90  grams  ( 100  grams  of 
broiled  meat),  sugar  5  grams  (butter  12  grams).  Second  Jural- fast :  mild  Rhine  wine. 
or  bouillon,  or  water  100  grams,  or  Port  wine  50  prams,  solid  food  50  grams  of  cold  meat 
and  20  grams  of  rye  bread.  Midday:  light  Rhine  wine  250  grams,  broiled  beef  150  to 
200  grams,  salad  or  vegetables  (cabbage)  50  grams,  cereal  100  grams  (bread  25  grams)  , 
fruit  100  grams.  Afternoon:  coffee,  with  milk  and  BUgar  as  in  the  morning.  Evening: 
mild  Rhine  wine  or  water  250  grams,  caviar  12  grams  I  Kiel  sprats  12  grams,  smoked 
salmon  18  grams,  2  softd>oiled  eggs  =  90  grams),  game  150  grams,  cheese  15  grams,  rye 
bread  20  grams   (fruit  100  grams). 

The  preceding  diet  list  of  Oertel's  contains : 

Albumin.  Fats.  Carbohydrates.  Water. 

160  grams  42.5  grams  117.5  grams  1,440  grams 

The  withdrawal  of  fluid  in  the  treatment  of  obesity  appears  to  have  found 
no  favor  in  this  Latest  plan.  It  is  of  especial  interest  to  note  tli.it  this  method, 
originating  in  Munich  (where  it  was  ostentatiously  advertised)  is  now  vigor- 
ously condemned,  as  is  evident  in  the  criticism  of  h\  v.  Hoesslin  based  upon 
a  very  rich  experience. 

As  the  result  of  his  observations  v.  Hoesslin  arrives  at  the  conclusion  that 
in  the  so-called  Oertel  cure  we  are  using  in  fact  a  Iruc  hunger  cure,  v.  Eo 
lin  even  believes  Jt  questionable  whether  in  antifat  treatment  the  reduction 
in  the  amount  of  fluid  plays  any  part.  He  does  not  regard  Oertel's  method 
as  a  eon  i  mi 'nil  able  one,  and  holds  the  -a  me  \  iew  in  regard  to  the  Banting  cure; 
for  though  he  looks  upon  its  effeel  in  depleting  fai  as  good,  its  action  upon 
the  general  condition  he  designates  as  had.  His  method  in  the  treatment  of 
obesity  consists  of  four  parts,  and  depends  upon  nutrition  by  a  pure  fat-albu- 
min diet,  modified  according  /<<  the  />rin<i/>!cs  proposed  Inj  me.  Without  here 
going  into  detail  in  regard  to  the  modifications  in  v.  Hoesslin's  diet  lists,  I 
will  -imply  emphasize  the  fad  that  he  doe-  full  justice  to  fat  in  the  treatment 
of  obesity,  and    that    he   pronounces  the  results  obtained    by   him    through   diet 

alone  to  he  very  satisfactory.  It  is  true  he  lavs  stress  upon  the  fact  that  these 
results  do  not  equal  those  attained  by  diet  combined  with  the  other  three  com- 
ponents of  his  obesity  treatment.  These  consist  in  the  simultaneous  stimula- 
tion of  metabolism  by  hydrotherapy,  the  augmentation  of  oxidation  proa 
by  increased  muscular  exercise,  and  finally,  the  administration  of  thyreoidin 
tablets. 

What  of  the  treatment  of  obesity  with  thyreoidin  tablets  as  mentioned  by 
v.   Hoesslin?     I  have  BUbjected  this  method  to  an  accurate  te8t,  anil  have  pub- 


176  OBESITY 

lished  the  results  in  the  Deutsche  medicinische  Wochenschrift,  1899,  p.  1. 
When  this  treatment  was  introduced  it  became  highly  popular,  but  it  proved 
by  no  means  so  harmless  as  many  at  first  maintained.  I  shall  content  myself 
with  the  following  statement  in  regard  to  it.  I  do  not  advise  thyreoid  treat- 
ment in,  obesity  because,  in  the  first  place,  the  loss  of  weight  produced  by  it  is 
quite  inconstant,  and  always  ceases  at  once  with  the  discontinuance  of  the 
thyreoid  preparation.  Further,  this  method  of  treatment  is  not  rational  be- 
cause the  danger  in  the  loss  of  body  albumin  is  a  considerable  one.  Finally, 
it  is  quite  unnecessary  because  we  are  in  possession  of  dietetic  rules  for  the 
treatment  of  obesity  which  are  as  successful  as  they  are  devoid  of  danger. 
This  view  in  regard  to  thyreoid  gland  treatment  in  obesity  seems  now  likely 
to  be  generally  accepted. 

In  regard  to  the  two  other  curative  factors  made  use  of  by  v.  Hoesslin, 
namely,  hydrotherapy  and  augmentation  of  the  processes  of  oxidation  In- 
increased  muscular  exercise,  there  can  be  no  objection  to  their  use  in  conjunc- 
tion with  an  appropriate  diet.  It  must  be  admitted  that  when  these  curative 
agents  are  wisely  regulated  by  an  able  and  experienced  hand,  and  are  indi- 
vidualized, the  result  is  not  only  hastened,  but  in  many  respects  heightened. 
E.  v.  Hoesslin,  as  physician-in-chief  of  the  institution  in  New  Wittelsbach  near 
Munich,  certainly  has  the  advantage  of  splendid  facilities  and  has  acquired 
great  experience.  But  with  the  remedial  agents  just  discussed  it  is  as  true 
as  it  is  of  the  dietetic  measures  that  a  permanent  result  may  only  be  expected 
when  the  persons  in  question  continue  their  muscular  exercise. 

What  is  the  character  of  the  muscular  movements  which  are  of  especial 
importance  in  the  treatment  of  obesity?  Those  especially  should  be  prac- 
tised which  will  influence  most  favorably,  and  to  the  greatest  extent,  the  total 
metabolism,  i.  e.,  muscular  movements  in  which  most  or  all  of  the  muscles 
are  brought  into  action,  as  in  the  so-called  free  exercises  of  German  turners 
and  in  exercises  with  gymnasium  apparatus.  The  former,  because  they  call 
for  only  a  comparatively  slight  use  of  power,  are  particularly  suitable  for 
persons  with  feeble  muscles. 

Muscular  exercises  of  this  kind  practised  in  the  open  air,  passing  grad- 
ually and  regularly  from  the  light  to  the  severe,  are  preferable  as  a  rule  to  the 
exercise  involved  in  games  or  sport.  The  latter  may  only  be  prescribed  for 
the  obese  when  they  can  be  practised  in  moderation,  and  when  they  call  for 
the  most  varied  action  of  all  the  muscles.  In  permitting  the  practice  of  any 
sport  we  must  make  sure  of  course  that  there  is  a  sound,  competent  heart  and 
normal  kidneys.  This  is  especially  true  of  hi  cycling,  which  is  now  in  such 
vogue.  But  for  obese  persons  of  active  habits,  the  best  form  of  exercise  is 
manual  work  performed  in  the  field  or  the  garden.  This  is.  after  all,  the 
most  natural.  Besides  this,  walking,  especially  in  a  region  of  diversified  scen- 
ery, mountain-climbing,  and  all  sorts  of  mountain  sports,  provided  always  the 
heart  is  normal,  are  factors  not  to  be  underrated  in  the  treatment  of  obesity. 
They  are  much  preferable  to  spas  and  water  cures,  but  need,  nevertheless,  to 
be  carefully  controlled.  A  weak  heart  which,  even  when  the  patient  is  at 
rest,  does  not  function  properly,  cannot  be  expected  to  endure  the  strain  of 
muscular  exercise  and  exertions  of  this  kind.     When  the  heart  is  weak,  passive 


TREATMENT  177 

muscular  exercise,  and,  best  of  all  massage,  are  especially  valuable.  By  light 
clothing,  the  consumption  of  heat,  and  with  it  the  metabolism  of  the  obese, 
may  be  decidedly  increased.  By  clothing  of  this  kind  muscular  exercise  is 
facilitated.  In  winter  it  is  advisable  to  wear  woolen  underclothing.  Unfor- 
tunately when  it  is  washed  it  generally  loses  its  porosity,  and  with  this  its 
greatest  advantage,  and  thus  becomes  merely  expensive.  In  summer,  on 
account  of  their  great  tendency  to  excessive  sweat  formation,  the  obese  mostly 
prefer  porous  cotton  underclothing. 

A  sensible  mode  of  life  in  which  moderation  in  eating  and  drinking  is 
maintained,  and  in  which  sufficient  muscular  exercise  is  secured,  permits  us 
to  predict  with  some  degree  of  certainty  that  no  superfluous  body  fat  will 
accumulate,  and  that,  where  already  present,  it  will  disappear.  If  an  indi- 
vidual predisposed  to  obesity  will,  after  ridding  himself  of  his  superfluous  fat 
in  this  manner,  adhere  to  the  prescribed  mode  of  life,  he  may  expect  that  no 
renewal  of  the  accumulation  of  fat  will  take  place  in  later  life. 

I  have  endeavored  in  this  article  to  suggest  the  methods  known  to  us 
to-day  of  which  we  may  avail  ourselves  in  assisting  the  obese  to  regain  their 
health  without  discomfort.  Nevertheless,  in  the  prognosis  the  physician  is 
not  to  give  way  to  illusions.  In  the  course  of  years  1  have  collected  a  con- 
siderable number  of  experiences  which  show  that  there  are  many  obese  per- 
sons who  prove  to  be  very  satisfactory  patients;  who,  regulating  their  mode 
of  life  in  accordance  with  the  condition  of  their  bodies,  improve,  and  may  be 
entirely  cured  within  a  short  space  of  time.  It  is  not  well,  however,  to  be  too 
sanguine.  Often  all  hope  is  shattered  by  the  epicurism  and  foolishness  of 
these  patients.  Many  of  them,  it  is  true,  will  submit  for  a  certain  time  to  the 
deprivations  and  obligations  to  which  their  condition  subjects  them,  but  will 
then  return  to  the  habits  which  have  produced  the  obesity.  If  they  belong  to 
the  minority  who  are  in  good  circumstances,  they  go  in  the  summer  time  to  a 
"cure"  which  they  expect  in  a  few  weeks  to  make  them  perfectly  well.  In- 
stead of  pursuing  the  course  of  life  which  experience  fias  shown  to  be  sensible, 
and  by  which  they  may  avoid  the  downward  path  to  which  their  condition 
inevitably  lead-,  they  quietly  pursue  their  sluggish  way.  For  eleven  month-  of 
the  year  they  commit  all  -ort-  of  dietetic  sin-,  and  then  in  the  twelfth  month 
submit  to  a  mineral  Bpring  treatment  and  bath  cure  which  is  to  cleanse  the 
body  and  wash  away  all  its  burdens.  I  adhere  to-day  to  the  opinion  which  I 
have  always  expressed  that  every  cure  of  this  kind,  as  well  as  every  drin:  treat- 
ment, particularly  by  means  of  purgatives  of  any  kind,  i-  to  he  rejected  in 
obesity.  This  is  particularly  true  of  the  treatment  which  Kisch  ha-  desig- 
nated a-  hi-  method   for  the  cure  of  the  plethoric  form  of  obesity  (  Ki-di.  "  The 

Cure  of  Obesity/'  Berlin,  1891,  p.  113,  et  seq.),  and  I  am  strengthened  in  my 

adverse  opinion  by  tl sample  which  Ki-ch  quotes  to  -how  the  efficacy  of  his 

method,  namely,  a  1..--  of  1 1  kilograms  and  IS  grams  of  weight  within  twenty- 
eight  days  in  an  uncomplicated  case  of  obesity  in  a  man  aged  forty-two  years 
and  weighing  1  in  kilograms  and  ".*>  grams.  This  procedure  is  by  no  mean- 
to  be  recommended.  The  cure,  a-  practised  by  Kisch,  consisted  (apart  from 
the  dietetic  treatment  which  in  the  main  corresponded  to  the  im  fat  treat- 
ment) in  the  use  of  Marienbad  mineral  water-  internally,  for  bathing,  in 
18 


178  OBESITY 

steam  baths,  exercise  amounting  to  25,000  steps  daily,  and  hydrotherapeutic 
measures.  It  is  true  that  Kisch  has  proven  it  to  be  possible  by  this  method 
to  become  lean.  But,  a  priori,  can  one  doubt  that  in  such  a  treatment  (the 
patient  lost  on  the  first  day  one  kilogram  and  25  grams)  muscle  as  well  as 
fat  is  lost?  The  loss  in  weight  by  this  treatment  is  not  always  so  great  as 
that  which  Kisch  attained  at  Marienbad  in  four  weeks.  It  varies  between 
3  and  13.2  per  cent,  of  the  patient's  weight;  on  the  average  it  amounts  to  6.7 
per  cent.,  which,  in  my  opinion,  is  more  than  is  desirable  in  the  rational  treat- 
ment of  obesity.     It  should  therefore  be  avoided. 

In  conclusion,  I  must  mention  the  dangers  which  confront  all  who  use 
acids,  particularly  vinegar,  a  practice  which,  unfortunately,  we  find  very  com- 
mon in  young  girls  who,  from  vanity  and  a  desire  to  remain  slender,  risk  their 
health  and  even  their  lives. 


MYXEDEMA 
WITH   SPECIAL   REFERENCE  TO   ORGANOTHERAPY 

By  C.   A.   EWALD,   Berlin 

HISTORY 

At  a  meeting  of  the  Congress  of  the  British  Medical  Association  at  Lon- 
don in  1875,  various  medical  curiosities  were  shown,  among  them  a  number 
of  patients,  mostly  women,  who,  on  account  of  their  peculiar  appearance  and 
behavior,  excited  the  greatest  interest.  At  first  glance  one  would  have  thought 
that  a  group  of  Eskimos  or  Samoans  was  present.  Their  swollen  faces  of 
strange  yellow  tint,  almond-shaped  eyes,  and  stupid  expression,  their  clumsy 
figures,  the  leathery  texture  of  their  skins,  the  scant  growth  of  hair,  and  their 
torpid  mental  state  made  them  a  truly  remarkable  spectacle.  One  could 
hardly  realize  that  these  were  children  of  sea-encompassed  Albion,  so  com- 
pletely in  them  had  the  characteristic  features  of  the  Anglo-Saxon  race  been 
eradicated.  As  explained  by  Dr.  William  Ord,  these  were  cases  of  myxedema. 
We  owe  the  recognition  of  these  cases,  and  their  classification  as  a  special 
pathological  group  to  be  differentiated  from  cretinism  and  imbecility,  to  two 
English  physicians,  Sir  William  Gull  and  Dr.  William  Ord  (in  is;:;  and 
1878).  The  latter  physician  was  also  the  fir.-t  t<»  designate  the  condition 
myxedema,  on  account  of  the  peculiar  muco-edematous  condition  of  the  in- 
tegument, and  Charcol  later  proposed  the  name  "  cachexie  pachydermique" 
which,  in  my  opinion,  is  more  suitable.  As  a  matter  of  fact,  the  mucus  con- 
tent of  the  skin,  contrary  to  the  assumption  <>f  the  iir>t  observers,  18  hut  slight, 
although  Shaw  believed  it  to  he  fifty  times  greater  than  in  the  normal  skin. 
The  general  thickening  of  the  skin  greatly  overshadows  this.  Eowever,  an 
aptly  chosen  name  soon  take-  root,  even  if  ii  be  not  quite  unobjectionable  (I 
need  only  refer  t<>  the  barbarous  word  "appendicitis"),  and  so  it  has  been 
with  the  term  "myxedema";  every  one  knows  nowaday-  whal  is  mean!  by  the 

term. 

Since  then  twenty-five  years  have  passed,  ami  numerous  cases  of  myxedema 
have  been  described,  particularly  in  England  ami  America.  The  peculiarities 
of  the  disease  have  been  thoroughly  studied,  ami  our  understanding  of  its 

nature   based    upon   this  study   has   led   to   therapeutic   BUCCess  a-    far   reaching 

ami  as  remarkable  as  any  in  the  entire  realm  of  medicine,  excepting  only 
Berumtherapy. 

In  Germany,  myxedema  i-  comparatively  rare.  I  am.  however,  in  a  posi- 
tion to  relate  the  history  of  a  very  characteristic  case: 

179 


ISO  MYXEDEMA 

The  patient,  a  woman  aged  fifty-five,  has  heen  known  to  me  for  six  years ; 
the  symptoms  of  the  disease  developed  slowly  and  insidiously,  and  for  a  long 
time  they  were  so  little  characteristic  that  it  was  hardly  possible  to  differen- 
tiate the  condition  from  the  ordinary  cachexia  of  old  age.  But  the  behavior 
and  appearance  of  the  patient  were,  even  at  that  time,  so  peculiar  that  I  had 
a  photograph  of  her  taken  which  is  here  reproduced  (see  Fig.  1).  Later, 
however,  the  typical  symptoms  appeared  (see  Fig.  2).  They  improved  and 
nearly  disappeared  under  specific  treatment  (thyreoid  extract),  but  returned 
after  some  time,  the  patient  having  discontinued  her  treatment.  Fig.  3  shows 
the  patient  in  this  stage  of  her  disease.1 

ETIOLOGY 

Regarding  etiology,  as  little  could  be  determined  in  my  case  as  in  other 
cases  of  myxedema.  .  A  tendency  to  nervous  diseases  and  depressing  influences 
of  a  psychical  nature  are  said  to  be  conducive  to  the  development  of  the  dis- 
ease. Whether  alcohol,  syphilis,  and  tuberculosis,  those  exterminators  of  the 
human  race,  play  their  part  in  this  disease  is  very  questionable,  although  sev- 
eral authorities  (Pel,  Greenfeld,  and  Byrom  Bramwell)  have  called  atten- 
tion to  the  occurrence  of  tuberculosis  in  the  families  of  myxedematous  patients, 
or  in  the  patient  himself.  Several  cases  in  the  same  family  have  also  been 
observed. 

The  sex  of  my  patient  confirms  the  general  experience  that  women  are 
attacked  in  the  majority  of  instances,  and  Sir  William  Gull  entitled  his  first 
communication,  "  On  a  Cretinoid  State  Supervening  in  Adult  Life  in  Women." 
Full  seven  years  after  the  first  publication  regarding  myxedema,  a  male  suffer- 
ing from  this  affection  was  observed  by  Savage  (1880).  In  1894,  in  a  com- 
pilation of  127  cases  of  myxedema,  Heinsheimcr  found  only  10  men,  i.e., 
7.8  per  cent. ;  and  this  proportion  would  about  correspond  to  the  ratio  if  we 
tabulated  all  the  cases  that  have  been  published  up  to  the  present  time. 

Typical  myxedema  is  a  disease  of  adults,  occurring  most  frequently  be- 
tween the  thirty-fifth  and  fiftieth  years  of  life.  It  is,  however,  by  no  means 
limited  to  these  ages,  but  may  occur  earlier,  as  the  so-called  infantile  myx- 
edema, or  even  later  (which  is  quite  rare). 

SYMPTOMS 

The  symptoms  of  myxedema  consist  of: 

1.  Changes  in  the  external  integuments  (skin,  hair,  nails),  and  the  absence, 
or,  more  strictly  speaking,  the  degeneration  of  the  thyreoid  gland. 

2.  Disturbances  of  the  cerebral  and  nervous  functions. 

3.  Disturbances  of  nutrition  (of  metabolism)  and  of  circulation. 

i  The  literature  up  to  1S90  is  almost  complete  in  C.  A.  Ewald's  "The  Diseases  of 
the  Thyreoid  Gland,  Myxedema  and  Cretinism,"  in  Nothnagels  "  Special  Pathology  and 
Therapy,"  xxii.  Part  I;  for  later  articles  sec  Ewald's  article  '"Organotherapy,"  in 
Mendel' 8  Jahresbericht  für  Neurologie  und  Psychiatrie. 


FlO.    1.  —  W.    M.,    Ar, i  i.    I  ■hi;  i  \-i  i.,ii  r;   Imu'iini    MtXKPICMA. 


Fig.  2. — W.  M.,  Aged  Fifty-two;  Advanced  Myxedema. 


Fig.  3. — \Y.    M.    \jOZD    In  n-iiii;n   ;    MYXEDEMA    in    im     StaOI     Ol     RSCOTXBI     UTTBB    THE 

Employment  01  39.2  Qrahs  o»   Chthsoioin. 


184  MYXEDEMA 

These  features  are  not  equally  developed  nor  even  all  present  in  every  case, 
and  my  case  was  no  exception  to  this  rule. 

Of  greatest  importance  in  the  diagnosis  of  the  disease  are  the  cutaneous 
symptoms.  They  make  it  possible  for  us  to  recognize  the  malady,  prima  vista, 
so  to  speak,  and  after  a  comparatively  brief  examination  of  the  patient.  They 
give  the  patient  the  characteristic  stamp  which  I  attempted  briefly  to  portray 
at  the  beginning  of  this  article. 

1.  Most  frequently  the  disease  begins  unnoticed  and  insidiously,  with  a 
gradual  swelling  of  the  skin,  at  first  in  the  face,  then  in  the  hands,  arms,  feet 
and  legs ;  finally  and  least  noticeably  upon  the  trunk.  In  the  cheeks,  around 
the  eyelids,  and  upon  the  chin,  puffmess  is  noticed ;  the  lips  and  nose  become 
swollen  and  thickened,  the  palpebral  fissure  is  diminished  by  the  swelling  of 
the  eyelids,  and  a  hard,  elastic  edema  of  the  whole  face  produces  a  stupid, 
dull  expression.  The  tongue  is  thick,  clumsy  and  too  large  for  the  mouth; 
the  soft  palate,  the  uvula,  and  the  postpharyngeal  Avail,  as  well  as  the  larynx, 
are  swollen.  Hence  the  voice  becomes  rough  and  hoarse  with  a  peculiar  deep 
sound.  The  gums  also  swell,  bleed  readily,  and  retract  from  the  teeth,  which 
have  a  tendency  to  caries  and  frequently  drop  out  without  any  change  of 
structure.  The  lobes  of  the  ear  are  also  coarse  and  misshapen.  Upon  both 
sides  of  the  neck  above  the  clavicle,  swellings  appear,  which  are  soft  to  the 
touch,  and  from  about  the  size  of  a  plum  to  that  of  a  hen's  egg.  These  pads 
are  not  due  to  swollen  glands,  but  consist  of  fat,  connective  tissue,  and  convo- 
lution of  vessels  (veins).  The  extremities  appear  swollen  and  shapeless,  the 
hands  like  paws ;  wider  shoes  and  larger  gloves  become  necessary. 

The  skin  is  pale  and  looks  anemic;  occasionally  it  has  a  marbled  appear- 
ance ;  to  the  touch  it  is  cold,  unelastic,  hard  and  coarse.  If  pressure  is  made 
with  the  finger  a  slight  impression  is  made,  but  the  pitting  does  not  remain. 
As  a  rule,  this  swelling  is  by  no  means  uniformly  distributed  over  the  entire 
body.  It  attacks  preferably  either  the  face  and  the  supraclavicular  region  or 
the  extremities.  Occasionally  it  disappears  temporarily  at  the  beginning  of 
the  disease  (Ord),  and  then  recurs,  wandering  here  and  there.  The  skin  is 
dry,  rough,  desquamates  decidedly,  and  not  even  by  means  of  diaphoretics  can 
sensible  perspiration  be  induced,  while  insensible  perspiration  is  lessened  from 
40  to  CO  per  cent,  in  comparison  to  the  normal.  The  nails  show  longitudinal 
fissures  and  become  brittle.  The  hair  of  the  head  and  eyebrows  falls  out, 
and  soon  large  areas  are  formed  which  are  perfectly  bald. 

Besides  these  striking  changes  there  is  a  further  defect  which  indeed  can- 
not always  be  determined  with  certainty  during  life,  but  which  in  my  patient, 
for  example,  was  readily  demonstrated;  I  mean  the  absence  of  the  thyreoid. 
In  place  of  the  lobes  of  the  gland  normally  situated  upon  both  sides  of  the 
wind-pipe,  the  smooth  wall  of  the  trachea  may  be  palpated  from  the  cricoid 
cartilage  to  the  jugulum.  I  shall  revert  later  to  this  remarkable  condition, 
and  to  its  importance  in  pathogenesis. 

2.  The  disturbances  of  the  cerebral  functions  mostly  set  in  with  headache, 
sometimes  with  a  feeling  of  anxiety,  and  a  heaviness  in  the  limbs.  The 
patients  move  about  slowly  and  with  uncertainty.  The  power  of  co-ordination 
is  diminished,  as  is  frequently  shown  in  the  attempts  at  walking.     The  patient 


SYMPTOMS  185 

then  conveys  the  impression  of  being  under  the  influence  of  a  high  grade  of 
nervous  irritability  with  severe  muscular  tremor,  so  that  it  is  impossible  to 
maintain  an  erect  attitude. 

The  patient's  appearance  is  peculiarly  quiet  and  suggests  mental  limita- 
tion, an  impression  which  is  increased  by  the  fact  that  the  head  is  mostly  bent 
forward  so  that  the  chin  is  held,  or.  more  correctly,  falls  upon  the  chest,  for 
the  patient  cannot  keep  the  head  erect.  The  power  of  thought  Lessens,  and 
its  exorcise  is  apparently  difficult.  There  is  loss  of  memory,  particularly  in 
regard  to  the  true  duration  of  the  illness;  now  and  then  actual  hallucinations 
appear.  Speech  itself  i-  peculiar,  being  monotonous  with  a  nasal  or  rough 
quality,  and  tin-,  combined  with  a  certain  tendency  of  the  patient  after  hav- 
ing once  begun  to  speak  to  continue  uninterruptedly  like  a  wound-up  clock- 
work, is  looked  upon  by  Ord  as  especially  characteristic.  I  must  admit  that 
this  latter  condition  has  not  yet  been  noticed  by  me  in  my  very  much  more 
limited  experience.  Finally,  actual  convulsion-  ami  coma  have  been  observed. 
The  reports  in  regard  to  reflexes,  cutaneous  sensation,  ami  electric  irritability 
vary.  In  my  case  no  disturbance  of  these  function-  was  present.  The  tendon 
reflexes  were  prompt,  ami  electric  irritability  both  for  the  I'aradic  and  constant 
current  was  normal.  The  sensation  of  cold,  and  the  lowered  body  tempera- 
ture which  is  the  cause  of  this,  may  be  considered  a-  due  in  part  to  the  nervous 
disturbances.  The  temperature  in  the  axilla  varies  between  96.8°  F.  ami 
98.6°  F.  The  patients  feel  "as  if  they  were  living  in  an  eternal  winter." 
Unquestionably,  this  sensation  of  cold  depend-  upon  the  inability  of  the 
patient-  to  regulate  the  body  temperature  so  a-  to  correspond  with  variations 
in  the  external  temperature;  they  sutler  particularly  in  cold  and  frosty 
weather.  On  the  other  hand,  there  is  deficient  energy  of  oxidation,  a  dimin- 
ished heat  production,  in  the  organism. 

This  lead-  n-  to  the  discussion  of  the  last  point: 

::.  Disturbances  of  metabolism  and  of  Ihr  circulation.  The  former  is 
decidedly  decreased.  The  area  or  KT-excrel  ion  as  well  a-  the  respiratory  metab- 
olism (Magnus-Levy)  is  decreased.  Albumin  is  occasionally  found  in  the 
urine,  sometimes  only  in  trace-,  sometimes  in  larger  amounts.  According  to 
ihr  observations  of  Byrom  Bramwell,  as  well  as  of  llun  ami  Prudden,  albumin 
is  found  in  about  L8  per  cent,  of  the  cases.  In  rare  instances  at  the  acme  of 
the  myxedematous  stage,  mucus  is  also  found  in  the  urine.  In  the  blood  there 
i-  a  slighl  oligocythemia  or  a  polycythemia.  In  women  there  is  amenorrhea. 
The  pulse  i-  -mall,  low  and  weak.  Hemorrhages  from  the  mucous  membranes, 
particularly  from  the  nose  and  mouth,  are  qoj   rare. 

I  have  now  sketched  the  mosl  important  symptoms.     I  omit  the  rarer  ones 

a-,   for  example,  synovitis  of  the  ki -joint,  premature  climacteric,  tremor  of 

the  eyelids,  contractures  of  the  hand-  and  feet,  salivation.  The  characteristic 
symptom-  of  the  affection  under  discussion  are  limited  to  tissue  changes,  par- 
ticularly of  two  organs,  the  -kin  ami  the  thyreoid  gland.  The  connective  ti-- 
sue  id'  the  corium  is  loosened,  its  individual  fibers  thickened  ami  hyperpla 
The  cell  nuclei  and  the  fibrillary  elements  of  the  gelatinous  substances  be- 
tween the  individual  fat  lohe-  are  increased,  h  seems  as  if  the  skin  were 
saturated  with  a  lluid  or  semi-fluid  Bubstance.     Whether  this  actually  con- 


186  MYXEDEMA 

sists  of  mucus,  i.  e.,  of  an  edematous  fluid  containing  considerable  amounts  of 
mucin,  is  not  yet  certain.  This  much,  however,  is  assured,  that  the  degree  of 
this  infiltration  may  vary  decidedly  in  individual  cases.  In  my  patient  there 
is  now  only  slight  swelling  of  the  eyelids  and  of  the  cheeks,  but  at  the  height 
of  the  disease  the  entire  face,  shoulder-girdle,  hands,  forearms,  and  feet  showed 
swelling  which  was  everywhere  unmistakable,  and  here  and  there  extreme. 
In  a  case  observed  by  Kast  (Ponfick)  the  thickening  of  the  skin  was  so 
extreme  that  numerous  fissures  formed,  with  intertrigo-like  excoriations 
which  were  followed  first  by  a  phlegmon  of  the  arm  and  later  by  a  general 
fatal  sepsis. 

In  the  internal  organs  usually  no  changes  are  found  apart  from  the  pre- 
viously mentioned  atrophy  of  the  thyreoid  gland,  but  occasionally  cirrhotic 
processes  in  the  liver  and  kidneys,  endarteritis  obliterans,  and  enlargement  of 
the  pineal  gland  have  been  noted. 

The  changes  in  the  thyreoid  gland  are  undoubtedly  the  most  remarkable 
feature  of  this  disease.  In  most  cases,  even  during  life,  we  observe  that  it 
is  impossible  to  palpate  the  lobes  of  the  thyreoid  gland  in  the  neck.  It  may 
be  said  that  this  condition  is  found  in  about  80  per  cent,  of  the  cases.  In 
some  instances,  however,  the  atrophy  of  the  gland  cannot  be  determined  with 
certainty,  and  in  a  few  an  enlargement  has  been  noted.  Yet  in  these  cases, 
in  so  far  as  accurate  observations  have  been  obtained,  there  has  always  been 
found  a  strumous  degeneration  of  the  organ,  which  may  also  have  resulted  in 
a  loss  of  function.  I  have  been  able  to  collect  36  reliable  autopsy  reports, 
in  33  of  which,  or  94.4  per  cent,  of  the  cases,  there  was  atrophy  of  the  thyreoid 
gland.  The  necropsy  reports  show  that  the  gland  substance  had  lost  its  char- 
acteristic structure,  and  had  been  changed  into  a  more  or  less  shrunken  rem- 
nant, of  hard,  fibrous  consistence  and  yellowish  white  color.  Connective  tissue 
proliferation  leads  to  destruction  of  the  parenchyma,  so  that  only  isolated  re- 
mains of  degenerated  alveoli  can  be  detected.  Very  recently  Ponfick  has 
reported  an  extremely  careful  histological  investigation  of  the  remains  of  the 
gland  in  a  well-developed  case  of  myxedema.  He  found  "  in  wide  areas  almost 
total  destruction  of  the  follicles;  here  and  there  were  the  remains  of  rudi- 
mentary alveolar  structures,  all  filled  with  colloid.  Besides  this  atrophy  there 
was  an  enormous  increase  and  thickening  of  the  connective  tissue  structure ;  in 
a  word,  a  picture  which  markedly  resembled  the  terminal  stage  of  degenera- 
tive i  n  tl  a  minatory  processes,  such  as  are  met  with  so  frequently  in  the  kidneys, 
liver,  etc." 

PATHOLOGY 

I  need  hardly  say  that  this  degeneration  of  the  thyreoid  gland  is  the  key  to 
the  entire  pathological  condition.  Atrophy  of  the  thyreoid  gland  is  not  only 
one  of  the  symptoms  of  the  disease;  it  is  the  causative  factor.  This  fact  is 
absolutely  certain  in  spite  of  occasional  objections.  Its  recognition  forms  a 
glorious  page  in  the  history  of  pathology.  We  owe  this  to  the  united  labors 
of  physiologists  and  clinicians,  the  fruit  of  which  is  a  therapy  which,  as  re- 
gards the  certainty  of  success,  may  be  placed  side  by  side  with  the  most  reliable 
remedies  of  our  therapeutic  armamentarium. 


PATHOLOGY  187 

I  shall  attempt  to  prove  this  in  a  few  words,  thereby  taking  an  opportunity 
of  referring  to  related  conditions,  namely,  to  sporadic  and  endemic  cretinism, 
to  infantile  myxedema,  and  to  the  so-called  cachexia  strumipriva. 

Two  observations  stand  out  prominently  like  landmarks  in  the  great  num- 
ber of  physiologic  and  clinical  experiments  and  communications  which  resulted 
in  the  establishment  of  the  importance  of  the  thyreoid  gland  in  the  causation 
of  myxedema.  First,  the  experiment  of  .M.  Schiff,  the  results  of  which  were 
for  a  long  time  discredited  and  even  ridiculed,  but  at  last  completely  proven. 
In  this  experiment  an  animal  was  subjected  to  thyreoidectomy,  which  under 
ordinary  circumstances  would  have  proved  fatal,  as  Schiff  had  previously 
shown  in  1859.  But  Schiff  found  that  the  animal  did  not  succumb  if  the 
thyreoid  gland  were  grafted  into  the  abdominal  cavity  or  under  the  skin,  the 
specific  constituents  of  the  gland  being  thus  preserved  for  the  organism.  Next 
came  the  important  communications  of  Kocher  and  Reverdin  who  observed 
after  the  extirpation  of  the  thyreoid  gland  in  man  a  condition  of  general 
cachexia  with  physical  and  mental  phenomena  which  show  a  marked  similar- 
ity to  the  symptoms  of  myxedema  just  described,  and  also  correspond  accu- 
rately to  the  phenomena  developing  in  an  animal  after  extirpation  of  the 
thyreoid.  In  other  words  cachexia  strumipriva,  produced  experimentally  or 
(in  man)  as  the  result  of  an  operation,  is  identical  in  nature  with  genuine 
myxedema.  Now  since  in  both  cases  the  same  defect  is  present,  namely, 
absence  of  the  thyreoid,  it  follows  that  the  resulting  insufficiency,  that  is.  the 
complete  loss  of  function  of  the  thyreoid  gland,  is  to  he  Looked  upon  as  the 
cause  of  these  pathological  phenomena. 

I  cannot  here  discuss  the  differenl  phases  which  the  evolution  of  this  view 
has  undergone.  But  one  stage  at  least  1  should  like  to  bring  into  prominence, 
for  it  -how-  how  difficult  the  proper  interpretation  of  an  experiment  may 
sometimes  he,  and  how  obscured  by  complicating  conditions. 

Some  investigators  did  not  bucc I  in  producing  the  symptoms  of  cachexia 

strumipriva  (or,  more  correctly,  cachexia  thyreopriva,  a-  we  are  not  speaking 
of  the  removal  <<(  a  goiter)  by  thyreoidectomy,  and  consequently  were  justified 
in  doubting  the  causal  relation  of  the  thyreoid  gland.  Then  Gley  showed 
that  besides  the  great  mass  of  the  thyreoid  there  are  in  animal.-  small,  super- 
numerary glands,  which  had  already  been  anatomically  described  by  Sand- 
strom.  These  extra  thyreoids,  if  not  removed  together  with  the  gland,  per- 
form vicariously  the  function  of  the  latter.  Only  after  this  circumstance  had 
been  taken  into  consideration  could  constant  results  he  obtained.  In  the 
-auie  manne!-  we  may  explain  those  observations  (which,  however,  are  in  the 
minority)    which  -how  that    in  some  cases  cachexia  strumipriva  did   not    follow 

thyreoidectomy  in  man.  This  is  because  parts  of  the  gland  were  not  removed 
at  the  opera!  inn  or  because  a  rapid  reproduction  of  the  gland  look  place.  Mut 
even  a  I'rw  isolated  and  trustworthy  cases  of  this  kind  would  not  overbalance 
the  enormous  uumber  of  positive  observations  t"  the  contrary. 

Hut  let  us  proceed  a  step  further.  All  over  the  world,  a-  i-  well  known, 
there  are  unfortunate  individuals  whose  mental  and  bodily  development  is 
retarded,  bo  that  they  present  a  -tupid  and  misshapen  appearance.  They  are 
called  cretins,  and  their  disease  cretinism.     From  the  fact  that  Buch  ill-fated 


1S8  MYXEDEMA 

persons  are  met  with  in  isolated  regions,  and  are  particularly  numerous  in 
certain  localities,  and  inasmuch  as  the  development  and  distribution  of  the 
disease  are  apparently  dependent  upon  the  condition  of  the  soil  and  the  water- 
supply  of  the  district  in  which  the  cretins  accumulate,  we  call  these  cases 
"  endemic  cretinism."  In  other  parts  of  the  world  they  are  only  occasionally 
met  with,  and  we  then  speak  of  them  as  cases  of  sporadic  cretinism.  In  these 
cases  as  in  myxedema  there  is  an  insufficient  development,  or  an  atrophy  and 
disturbance  of  function  of  the  thyreoid  gland.  Hence  we  speak  of  them  as  an 
athyreosis  chronica,  in  contrast  to  the  results  produced  experimentally  in  ani- 
mals, or  after  loss  of  the  thyreoid  by  operation  in  man  in  whom  this  state  may 
be  called  cachexia  thyreopriva. 

Accurate  observation  and  study  of  the  cases  belonging  to  this  group  show 
that  endemic  cretinism  is  a  condition  of  physical  and  intellectual  degenera- 
tion, which  occurs  only  where  there  are  local  predisposing  causes,  and  a  degen- 
eration of  the  thyreoid  gland  produced  by  these  or  going  hand  in  hand  with 
them.  The  disease  begins  its  development  even  in  fetal  life.  Sporadic  cre- 
tinism, on  account  of  its  resemblance  to  myxedema  of  adults,  is  in  early 
life  also  designated  as  infantile  myxedema.  In  these  cases  we  find  mental 
weakness  even  to  idiocy.  Like  actual  typical  myxedema,  it  is  an  occa- 
sional affection  of  the  thyreoid  gland  with  consequent  loss  of  function,  i.  e.,  a 
disease  not  limited  to  a  definite  region.  The  course  of  genuine  cretinism,  as 
well  as  myxedema,  is  a  very  chronic  one,  lasting  for  decades,  so  that  a  cretin 
may  attain  relatively  old  age  provided  he  does  not  die  of  some  intercurrent 
disease.  Cases  of  sporadic  cretinism  (infantile  myxedema)  have,  as  a  rule,  a 
briefer  duration  of  life,  and  if  not  ameliorated  by  treatment  scarcely  survive 
the  third,  at  most  the  fourth,  decade.  Cachexia  thyreopriva  runs  a  subacute 
course,  and  unless  relieved  by  medical  aid  terminates  in  death  after  a  com- 
paratively short  time,  at  the  longest  four  or  five  years ! 

THERAPY 

This  is  not  the  place  in  which  to  discuss  the  clinical  symptoms  of  these 
diseases;  that  degeneration  of  the  thyreoid  gland  is  unquestionably  the  causa- 
tive factor  in  all  of  them  is  the  only  circumstance  important  for  us.  This  is 
clear  not  only  from  the  general  correspondence  of  the  external  pathologic  phe- 
nomena, but,  in  particular,  from  the  results  of  therapy  founded  especially 
upon  the  knowledge  of  the  causal  role  of  the  thyreoid  gland  in  these  cases. 
The  results  of  thyreoid  therapy  have  proven,  a  fortiori,  that  the  common  cause 
of  these  diseases  is  an  absence  of  function  of  the  thyreoid,  by  which,  it  may  be 
remarked  in  passing,  they  differ  from  goiter  or  struma. 

Properly  speaking,  in  these  cases  we  are  dealing  with  a  substitutiontherapy, 
replacing  the  lost  or  deficient  glandular  secretion  by  the  administration  of  the 
glandular  substance  or  its  extracts. 

The  surprising  experiments  of  Schiff,  previously  mentioned,  actually  com- 
pelled the  application  of  these  principles  in  the  human  subject,  and  Bircher 
in  1890  by  implantation  of  a  human  thyreoid  in  a  woman  with  cachexia 
strumipriva   first   succeeded   in   obtaining   a   curative   result.     Shortly   after 


THERAPY  189 

Horslev  proposed,  in  place  of  the  human  gland,  to  utilize  the  thyreoid  of  the 
sheep  in  myxedema  and  cretinism,  and  Bettencourl  and  Serrano  noted  a  rapid 
improvement  in  a  woman  with  myxedema,  in  whose  abdomen  they  engrafted 
one-half  of  a  sheep's  thyreoid.  When  Murray,  instead  of  employing  the  entire 
gland,  subcutaneously  injected  its  glycerin  extract,  and  Mackenzie  in  1892 
administered  the  fresh  gland  or  its  extract  internally  with  the  same  effect, 
and  other  observers  showed  that  the  dried  glandular  substance  in  tablet  form 
acted  in  the  same  manner,  the  therapy  of  myxedema  and  of  the  related  patho- 
logic conditions  previously  mentioned  became  a.s  simple  as  it  was  reliahle. 
In  fact,  reports  came  from  all  quarters  regarding  the  almost  remarkable  action 
of  this  "organotherapy,"  which  was  particularly  effective  in  myxedema,  in 
infantile  myxedema,  and  in  cachexia  strumipriva.  while  endemic  cretinism. 
owing  to  its  nature  could  only  be  benefited  to  a  slighter  extent.  The  tablets 
which  were  administered  were  so  prepared  as  to  dosage  that  each  tablet  corre- 
sponded to  0.25  gram  of  the  glandular  substance;  these  were  given  in  increas- 
ing doses  of  from  3  to  7  or  10  tablets  per  day.  until  (early  or  later)  symptoms 
of  intoxication,  extreme  or  mild  (the  symptoms  of  so-called  thyreoidism) 
appear. 

It  cannot  he  denied  that  the  use  of  the  entire  gland  has  certain  disadvan- 
tages, on  account  of  the  varying  amount  of  active  substance  in  the  individual 
gland  or  tablet,  the  admixture  of  products  of  decomposition,  etc.  Obviously 
it  would  be  desirable  to  isolate  and  to  utilize  the  specific  active  substance- 
There  have  been  numerous  trials  in  this  direction.  At  one  time  it  was 
hoped  that  the  desired  body  could  be  obtained  in  the  form  of  a  ferment,  at 
another  time  it  was  supposed  that  it  could  lie  secured  as  a  fixed  chemical  com- 
bination from  the  group  of  profeid  substances  or  even  as  an  alkaloid.  T  must 
mention  that  S.  Fraenkel,  in  1895,  isolated  a  Bubstance  belonging  to  the 
guanidin  group  with  the  empiric  formula.  ( ',;IIn  NT80B,  which  he  called  "  thyreo- 
antitoxin,"  and  Drechsel  and  Kocher,  Jr..  isolated  similar  combinations  from 
the  gland.  Then  Baumann,  in  1896,  made  the  surprising  discovery  that  the 
gland  contained  considerable  amounts  of  iodin.  and  that  this  iodin  was  found 
in  combination  with  organic  substances,  chiefly  in  his  opinion  with  albumin, 
and  to  a  -mailer  extent  with  globulin.  This  body  Baumann  called  iodothyrin, 
later  thyreoiodin,  and  .-bowed  that  from  the  pures!  thyreoiodin  9.3  per  cent. 
of  iodin  could  be  obtained  in  a  crystalline  form,  [nvestigators  are  not  yet  quite 
unanimous  a-  to  the  true  nature  of  thi>  thyreoiodin.  Tambach  assumes  that 
the  iodin  is  combined  with  various  albumin  bodies,  and  that  iodothyrin  forms 
only  a  part  of  the  iodin-containing  substances  of  the  thyreoid  gland.  Accord- 
ing to  Oswald,  the  iodin  combined  with  albumin  has  the  character  of  globulin, 
for  which  reason  he  called  it  thyreoglobulin.  From  this,  by  long-continued 
pep-in  digestion,  iodothyrin  and  iodin-containing  albumoses  and  peptone-  can 
he  -plit  oil'.  Besides  these,  a  nucleoproteid  i<  -aid  t<>  occur  which,  however, 
due-  not  possess  the  -peciiic  actii.n  of  the  gland.  Blum  denies  the  presence 
of  iodothyrin  a-  a  primary  constituent;  he  thinks  it  is  not  preformed  hut  is 
an  artificial  cleavage-product.  However  this  may  be.  Baumann  in  associa- 
tion with  IJoo-  seemed  to  prove  that  thyreoiodin  possesses  the  specific  proper- 
tie-  of  the  natural  gland,  and  acts  a-  a   -ul.-titute   for  it-  curative  effects;    it 


190  MYXEDEMA 

also  possesses  the  same  toxic  action,  but  lias  the  advantages  of  a  more  exact 
dosage  and  absolute  purity.  These  opinions  were  soon  confirmed  by  others 
(Hofmeister,  Ewald,  Hennig,  Goldmann,  and  others),  so  that  there  can  be 
no  doubt  that  thyreoiodin  may  be  employed  in  place  of  the  natural  gland. 
Whether  it  is  actually  an  equivalent  for  the  complete  gland  appears  doubtful 
from  the  investigations  of  Gottlieb  and  Jaquet,  who  observed  in  a  number  of 
dogs  after  thyreoidectomy  that  thyreoiodin  alone  did  not  keep  the  animals 
alive,  while  Gottlieb  by  administering  an  extract  from  the  complete  gland 
(thyraden),  and  Jaquet  by  a  substance  called  by  him  aiodin  (a  tannin  precipi- 
tate of  the  extract  of  the  gland  with  physiological  salt  solution)  succeeded 
in  sustaining  them.  I  might  also  mention  that  Cunningham  in  England 
isolated  a  so-called  colloid  substance  from  the  gland  which  is  analogous  to 
Baumann  s  thyreoiodin,  i.  e.,  the  contents  of  the  acini  after  previous  peptic 
digestion  of  the  gland  tissue.  He  is  consequently  of  the  opinion  that  this 
colloid  is  the  true  active  extractive  product  of  the  gland  cell,  while  Oswald 
believes  it  to  be  a  mixture  of  thyreoglobulin  and  nucleoproteid.  In  a  similar 
manner,  McLennan  produced  a  preparation  from  iodoglobulin  and  thyreo- 
iodin which  has  received  the  name  thyreoglandin.  In  view  of  all  this  it  is 
obvious  that  the  nature  of  the  specifically  active  substance  of  the  gland  has 
by  no  means  been  definitely  decided;  on  the  contrary,  each  day  brings  new 
reports  and  new  views. 

This  is  true  also  of  another  highly  interesting  discovery  which  science 
owes  to  Baumann,  who  was  unfortunately  too  early  removed  from  his  sphere 
of  activity.  In  a  comparative  estimation  of  the  iodin  contents  of  glands, 
some  of  which  were  procured  from  Freiburg  and  some  from  Hamburg  and 
Berlin,  it  was  shown  that  the  iodin  contents  of  the  former  were  considerably 
less  than  in  the  glands  brought  from  the  two  last  mentioned  cities.  The 
glands  obtained  from  Freiburg,  in  the  same  parts  by  weight,  averaged  2.5 
milligrams  of  iodin;  those  from  Hamburg  3.83  milligrams,  and  those  from 
Berlin  6.6  milligrams ;  in  the  investigations  in  North  America  made  by  Gideon 
Wells,  the  iodin  contents  of  20  glands,  some  from  Chicago,  some  from  Balti- 
more, Boston,  New  York,  etc.,  averaged  10.79  milligrams.  Now,  in  Frei- 
burg goiter  is  endemic  and  frequent,  in  Berlin  and  Hamburg  comparatively 
rare,  in  America  almost  unknown.  What  can  be  more  reasonable  than  to 
connect  the  slight  amount  of  iodin  in  the  glands  from  Freiburg  (where,  as 
may  be  remarked  in  passing,  goiter  is  found  conspicuously  often  even  in  the 
new-born  and  in  young  children)  with  the  prevalence  there  of  goiter?  For 
many  years  strumous  degeneration  has  been  referred  to  a  lack  of  iodin  in  the 
water,  in  the  air,  in  the  food,  though  no  convincing  proof  of  this  has  been 
established.  Here,  for  the  first  time,  we  seem  to  have  analytic  evidence  of  the 
influence  of  iodin  upon  the  development  of  goiter,  or,  more  correctly,  the 
relations  of  the  iodin  contents  of  the  thyreoid  gland  to  goiter.  I  expressly  say 
"  seem  to  have  evidence,"  for  to  make  this  assumption  a  certainty  more  com- 
prehensive investigations  are  necessary,  and  I  am  forced  to  admit  that  Oswald 
made  numerous  analyses  of  glands  from  Switzerland  and  from  the  regions 
where  goiter  occurs  endemically  and  has  demonstrated  the  exact  opposite; 
namely,  that  the  amount  of  iodin  in  glands  from  this  district  was  greater  than 


THERAPY  191 

in  those  obtained  elsewhere,  while,  on  the  other  hand,  Rositzki's  researches  in 
Styria  confirmed  Baumann's  reports. 

No  matter  how  diverse  the  manufactured  preparations  may  be,  their  use 
evidently  checks  the  previously  described  symptoms  of  myxedema,  which  give 
place  to  complete  or  almost  complete  health;  therefore  all  must  contain  the 
active  substance,  though  perhaps  some  more  than  others.  The  skin  becomes 
soft,  smooth  and  elastic;  the  edematous  infiltration — the  myxedema — disap- 
pears; the  hair  which  has  fallen  out  is  renewed.  The  general  health  returns 
to  the  norm,  vigor  and  activity  take  the  place  of  the  preceding  debility  and 
indolence — briefly,  so  complete  a  transformation  in  tbe  condition  of  the  patient 
takes  place  that  anything  more  extraordinary  can  hardly  be  imagined.  The 
same  is  also  true,  mutatis  mutandis,  in  the  conditions  previously  described, 
viz. :  infantile  myxedema,  cachexia  thyreopriva,  an  abortive  form  of  myx- 
edema which  has  been  designated  "  myxoedeme  fruste,"  and  to  some  extent 
also  in  cretinism.  To  enter  minutely  into  this  subject  would  cany  us  too 
far,  hence  we  will  only  remark  that  the  influence  of  thyreoid  preparations 
upon  the  length  and  caliber  of  the  bones  in  infantile  myxedema  has  been  ob- 
served, and  to  a  certain  extent  demonstrated,  ad  oculis,  by  means  of  radioscopy. 

We  noted  the  curative  effect  of  this  remedy  upon  myxedema  in  my  patient. 
As  time  has  gone  on  the  preparations  of  various  English  and  German  firms 
have  been  administered,  as  well  as  thyreoiodin  pastilles,  all  with  good  results 
which,  however,  Lasted  only  as  long  as  the  drug  was  given. 

After  discontinuing  the  administration  of  the  remedy  for  some  time — in 
my  case  for  a  few  months — we  must  always  return  to  it.  as  signs  of  myx- 
edematous cachexia  always  recur.  These  usually  consist  of  chilliness,  malaise, 
and  slight  swellings  in  the  face;  occasionally,  however,  severe  symptoms  of  de- 
pression appear,  particularly  of  a  psychic  nature.  This  is  not  to  be  wondered 
at,  as  our  Bubstitutiontherapy  «Iocs  not  rool  up  the  evil,  hut  only  re-supplies 
some  necessary  products  for  metabolism,  and  for  this  reason  the  medication 
musl  be  persistently  carried  on.  At  times  the  remedy  becomes  tmneccesary, 
and  it  may  be  discontinued  for  a  considerable  interval,  because  a  certain 
reserve  accumulates,  which,  after  the  cessation  of  the  specific  therapy;  is  only 
gradually  utilized  and  consumed  by  the  organism.  The  same  is  also  true, 
according  to  our  present  experience-,  in  cachexia  strumipriva,  while  in  infan- 
tile myxedema  and  cretinism  this  effect  doc-  not  occur,  and  from  the  begin- 
ning we  musl  carry  on  the  thyreoid  therapy  almost  continuously. 

One  of  my  patients,  a  highly  cultured  woman,  who  has  I o  taking  thyreoid 

extract  for  five  year-,  wrote  me  as  follow-:  "  I  may  Bay  thai  (inconceivable 
as  it  may  appear)  under  organotherapy  the  system  becomes  decidedly  accus- 
tomed to  the  taking  of  thyreoid  gland,  so  that  its  therapeutic  effect  is  weak- 
ened, and  the  doses  musl  be  constantly  increased  if  improvement  is  to  be 
expected.  On  the  other  hand,  when  we  consider  the  toxic  action,  the  debility 
and  tiring  of  the  heart,  the  damage  to  the  stomach,  etc.,  it  appears  that  one 
does  not  become  accustomed  to  it  ;  the  longer  the  drug  is  administered  the 
irrealer  the  susceptibility."  The  latter  remark  point-  to  the  secondary  effects 
of  thyreoidihcrapy,  effects  which,  after  prolonged  use  of  the  drug,  appear  to  1».' 
more  or  less  severe. 


192  MYXEDEMA 

This  secondary  condition  has  been  designated  thyreoidism;  the  disturb- 
ances may  be  separated  into  the  nutritive  and  the  nervous.  The  urine  in- 
creases in  amount,  and  its  X-containing  constituents,  as  well  as  the  chlorids 
and  phosphates,  are  increased.  The  body-weight  decreases  and,  as  was  first 
shown  by  Wendelstadt,  not  over  |  of  the  loss  in  weight  is  of  the  body  albumin; 
the  remainder  is  a  decrease  of  fat  and  water,  so  that  the  increased  combustion 
of  fat  may  be  referred  to  increased  oxidation  (Magnus-Levy).  In  this  process 
oxidation,  during  and  for  some  time  after  the  use  of  thyreoid,  may  rise  10  to 
20  per  cent,  above  the  former  values;  there  is  therefore  an  increased  metab- 
olism. As  a  nervous  symptom  we  note  primarily  a  decided  increase  in  pulse 
frequency  and  cardiac  palpitation,  which  may  be  looked  upon  as  a  definite 
indication  that  the  dose  is  too  large.  After  this  headache,  nausea,  vomiting, 
and  general  debility  may  occur.  Sometimes  these  symptoms  increase  to  an 
alarming  extent,  and  formerly,  when  this  condition  was  not  sufficiently  under- 
stood, even  fatal  cases  were  observed.  Therefore,  when  these  symptoms 
appear  (which  may  be  soon  or  late,  according  to  individual  susceptibility) 
thyreoid  preparations  must  be  immediately  stopped,  and  the  treatment  be 
interrupted.  These  toxic  symptoms  will  then  shortly  disappear  without  causing 
permanent  injury.  This  teaches  the  lesson  that  these  preparations  should 
not  be  used  except  on  the  advice  and  under  the  supervision  of  a  physician, 
and  their  sale  by  an  apothecary  except  upon  prescription  should  be  prohib- 
ited. How  far  thyreoidism  is  a  phenomenon  of  specific  intoxication,  and 
how  far  toxic  products  of  decomposition  generated  during  the  manufacture  of 
the  preparations  are  concerned  in  it,  is  doubtful.  Fortunately,  we  have  lately 
become  able  to  combat  these  symptoms  of  thyreoidism,  or  better,  to  prevent 
their  appearance;  as  Mabille  has  proposed,  we  administer  simultaneously  with 
the  thyreoid  preparations  small  doses  of  arsenic,  either  as  Fowler's  solution  or 
as  arsenious  acid.  As  a  matter  of  fact,  in  my  case  I  administered  no  less 
than  962  tablets  without  any  deleterious  effects,  and  during  three  months  I  gave 
3  drops  of  Fowler's  solution,  i.  e.,  upon  the  whole  a  minimal  amount  of  0.16 
gram  of  arsenious  acid. 

We  may  consider  it  as  definitely  settled  that  we  are  able  by  means  of  sub- 
stitutiontherapy  and  only  in  this  way  to  influence  the  entire  constitution  to 
such  a  surprising  extent,  in  the  pathologic  conditions  which  depend  upon 
atrophic  or  degenerative  changes  in  the  thyreoid  gland.  We  should  mention 
here  also  the  value  of  thyreoid  extract  in  the  abortive  forms  of  myxedema 
which  Hertoghc  has  described  under  the  designation  "  myxoedeme  fraste." 

The  use  of  thyreoid  preparations  should  also  be  considered  in  local  dis- 
ease of  the  thyreoid  gland,  namely,  in  the  treatment  of  goiter.  Although  suc- 
cess in  treatment  is  here  limited  to  the  so-called  parenchymatous  goiters  of 
youth,  i.  e.,  to  that  form  of  goiter  which  is  not  so  much  the  result  of  degenera- 
tive change  as  of  a  hypertrophic  condition  of  the  glandular  tissue,  their  use  is 
here  of  great  value,  v.  Bruns  was  the  first  to  employ  thyreoid  gland  prepara- 
tions in  simple  goiter  with  the  idea  of  diminishing  the  labor  of  the  hyperactive 
gland.  For  it  is  self-evident  that  in  such  cases  there  is  an  increased  demand 
in  the  organism  for  the  product  of  the  secretion  of  the  gland,  either  because, 
from  some  unknown  disturbance  of  metabolism,  more  thyreoiodin  was  required 


THERAPY  193 

and  so  consumed  by  the  organism,  or  because  the  supply  of  iodin  was  deficient 
while  the  activity  of  the  gland  was  especially  active,  thus  leading  finally  to 
hypertrophy  of  the  organ,  v.  Brnos,  in  fact,  observed  a  decided  diminution 
in  the  goiters  after  the  administration  of  comparatively  small  doses,  and 
Ewald,  Stabel,  and  others  in  Germany  obtained  similar  results.  Wells  in 
1897  compiled  584  cases  of  simple  goiter  which  were  treated  with  different 
thyreoid  extracts,  of  which  cases  475,  i.  e.,  about  82  per  cent.,  were  improved. 
Nevertheless,  in  my  experience,  the  cure  is  never  complete;  that  is,  the  goiter 
does  not  completely  disappear,  although  v.  Brims  reports  this  result  in  about 
8  per  cent,  of  his  cases.  As  has  been  already  stated,  the  best  results  are  seen 
in  youthful  individuals  in  whom  the  goiter  has  not  existed  for  too  long  a  time. 
The  older  the  patient  and  his  goiter  the  slighter  the  changes  which  may  be 
observed  in  the  gland  in  favorable  eases  even  after  four  to  six  days  of  treat- 
ment with  thyreoid  preparations.  Usually,  however,  this  become-  noticeable 
only  during  the  second  and  third  weeks  of  treatment.  A  diminution  in  the 
circumference  of  the  neck  of  from  I  to  6  centimeters  is  frequent;  greater  re- 
duction than  this  is  exceptional.  Even  in  these  cases,  after  discontinuance  of 
the  remedy  relapses  occur,  so  that  small  doses  must  be  repeated  from  time  to 
time. 

I  have  the  history  of  two  girls,  aged  nineteen  and  twenty-one  years  re- 
spectively, the  circumference  of  whose  necks  after  the  use  of  thyreoid  prepara- 
tions was  reduced  in  one  from  37.6  to  35.1  centimeter-,  and  in  the  other  from 
33.5  to  32.1  centimeters.  Symptoms  of  thyreoidism  did  not  appear.  I  must 
not  fail  to  mention  that  equally  favorable  results  have  been  obtained  with 
thymus  preparations  by  Mikulicz  and  Reinbach. 

The  conditions  are  very  differenl  in  another  disease  which  also  implicates 
the  thyreoid  gland:  (Irarrs  disease.  In  this  affection  enlargement  of  the 
thyreoid,  as  is  well  known,  is  one  of  the  three  cardinal  symptoms  of  the  dis- 
,,;,M. — goiter,  exophthalmos,  tachycardia.  Bui  here  we  are  no  Longer  dealing 
with  a  vicarious  or  compensatory  labor  hypertrophy  of  the  gland,  hut  with  an 
active  increase  of  it-  secretion,  which  lead-  to  the  phenomena  of  thyreoidism 
occurring  in  the  course  of  the  disease.  The  ose  of  thyreoid  preparation-:  in 
this  malady  is  contraindicated,  even  if  we  omil  entirely  from  consideration  the 
fact  that  the  cause  of  Graves'  disease  is  not  to  he  found  in  an  affection  of  the 

thyreoid   gland    alone.      We   know   that    it-  cause   i-   multiform    and    that    other 

organ — as  i-  shown  by  the  cases  without  goiter — especially  the  sympathetic 
nervous  system,  are  implicated.     A-  a  matter  of  fad  all  caution-  and  unbiased 

observers  have  been  convinced  of  the  complete  failure  of  thyreoid  therapy  in 
Basedow's  disease  (exophthalmic  goiter).  Indeed  it  ha-  been  noticed  that 
it-  u-e  i-  not  only  useless,  but  often  produce-  a  decided  aggravation  of  the 

symptom-. 

Although  we  have  up  to  this  point  discussed  the  administration  of  thyreoid 
preparations  only  as  true  substitutiontherapy  in  diseases  in  which  a  disturb- 
ance of  function  of  the  thyreoid  can  be  demonstrated,  ye\  the  li-i  of  the  uses 
of  the  remedy  ha-  by  no  mean-  been  exhausted.  We  know  of  other  dis- 
eases, or  disease  groups,  In  which,  based  upon  the  pharmacodynamic  action 
of  thyreoiodin,  this  remedy  ha-  been  employed  with  more  or  Less  success.     I 

14 


194  MYXEDEMA 

have  stated  before  that  the  employment  of  thyreoid  preparations  increases 
metabolism,  and  causes  a  decrease  in  the  fat  of  the  organism ;  this  has  been 
experimentally  proven.  What  was  more  natural  than  to  attempt  a  cure  of 
obesity  by  this  means?  Y.  Davies  in  America,  Leichtenstern  and  Ewald  in 
Germany,  were  the  first  to  publish  favorable  results  of  this  kind.  They  ob- 
tained in  obese  persons  reductions  in  weight  of  5  kilograms  and  more  in  a 
few  weeks  without  any  special  restriction  of  the  food,  and  without  producing 
marked  debility,  restlessness,  fatigue,  etc.  This  condition  is  due,  as  already 
remarked,  to  an  increased  combustion  of  carbohydrates  and  fat,  while  albumin 
decomposition  is  but  little  affected.  Schrödt  has  lately  published  a  case  in 
which  a  loss  of  16  kilograms  of  weight  occurred  in  an  obese  person,  and,  as 
was  shown  by  carefully  conducted  investigations  of  metabolism,  this  was  almost 
wholly  due  to  combustion  of  fat.  The  results  are  even  better  if  the  diet  is 
regulated  simultaneously,  i.  e.,  the  fats  and  carbohydrates  limited  to  a  certain 
extent  without,  however,  insisting  on  a  dietetic  cure  for  the  reduction  of  fat 
in  the  strict  sense  of  the  word.  Cabot  has  collected  145  cases  of  this  kind, 
and  reports  favorable  results  in  all  but  6  cases,  v.  Noorden,  who  is  not  well 
disposed  to  thyreoid  treatment  in  obesity,  nevertheless  observed  among  14 
patients,  who,  in  the  course  of  four  or  five  weeks,  had  taken  upon  the  average 
3  to  4  tablets  per  day,  a  reduction  in  weight  of  5.4,  6.0,  and  7.8  kilograms, 
and  had  only  one  complete  failure.  In  thyreoiodin  we  should,  therefore,  pos- 
sess an  almost  ideal  remedy  for  obesity  if  only  it  were  always  effective.  Ee- 
ports  of  failure  are,  however,  not  wanting,  and  in  several  cases,  instead  of  the 
desired  loss  of  weight,  symptoms  of  thyreoidism  have  appeared.  This  latter 
condition,  with  or  without  a  simultaneous  reduction  of  body  fat,  has  been  apt 
to  supervene  when  the  laity,  without  professional  advice,  have  used  the  thyreoid 
preparations  either  too  long  or  in  too  large  doses.  In  another  article,  in  re- 
ferring to  a  case  of  psoriasis  treated  by  the  thyreoid  preparations,  I  have  dis- 
cussed the  question  asked  by  Hertoghe,  whether  success  or  failure  in  these  cases 
does  not  depend  upon  the  condition  of  the  thyreoid  gland  of  the  affected  indi- 
vidual ;  i.  e.,  the  treatment  is  only  successful  in  cases  in  which  the  obesity 
(or  the  skin  disease)  is  one  of  the  manifestations  of  an  affection  produced  by 
disturbance  of  the  function  of  this  organ,  as  the  gland  certainly  has  a  decided 
influence  upon  metabolism. 

There  can  be  no  doubt,  as  has  been  determined  from  observations  in  myx- 
edema, of  the  effect  of  thyreoid  in  trophic  processes  of  the  shin.  Hence  thyreoid 
preparations  are  administered  in  various  skin  diseases,  lichen  planus,  prurigo, 
adenoma  sebaceum,  ichthyosis,  xeroderma,  lupus,  and,  above  all,  in  psoriasis; 
of  course  here  also  the  success  is  varying  and  uncertain.  In  some  quite  chronic 
cases  I  have  seen  conspicuous  improvement,  and  it  is  not  too  much  to  say  a 
cure;  in  others  there  was  no  result  in  spite  of  treatment  for  several  months. 
In  the  last  case  successfully  treated,  a  spare  man,  aged  fifty-three,  whom  I 
showed  at  the  meeting  of  the  Berlin  Medical  Society  on  July  18,  1900,  the 
thyreoid  gland  could  not  be  palpated.  This  man  had  a  persistent,  freely 
desquamating  eruption,  appearing  in  large  blotches  upon  the  trunk  and  ex- 
tremities, for  the  cure  of  which  various  remedies  had  been  unsuccessfully 
employed  for  years.    After  the  administration  for  three  months  of  thyreoiodin 


THERAPY  195 

tablets  with  arsenic — he  received  during  this  time  450  tablets  which  contained 
0.25  gram  of  iodothyrin  and  0.16  gram  of  arsenious  acid — the  eruption 
almost  disappeared,  being  replaced  by  small,  isolated  areas  of  about  the  size 
of  a  silver  three-cenl  piece,  and  by  natural,  smooth,  pink  skin.  Of  154  cases 
collected  by  Cabot,  63  were  improved,  53  unimproved,  and  22  aggravated. 
This  is  greatly  in  favor  of  my  view  previously  expressed  regarding  the  connec- 
tion between  these  diseases  of  the  skin  and  disturbances  in  function  of  the  thy- 
reoid gland  :  for  Wells,  in  a  case  of  scleroderma  in  a  woman  aged  fifty-one 
who  had  suffered  for  about  one  year  from  the  affection,  found  the  thyreoid 
-land,  posl  mortem,  to  be  greatly  atrophied,  so  that  in  the  fresh  condition  it 
weighed  only  14  grams  and  when  dried  only  3.23  grams.  The  total  amount 
of  iodin  was  only  2.94  milligrams,  i.e.,  only  about  one-fourth  of  the  normal. 
Microscopically  the  connective  tissue  was  greatly  increased,  the  intima  of  the 
glandular  vessels  was  proliferated,  the  lumen  of  the  acini,  for  the  mos!  part 
without  colloid,  changed  into  small  cysts  which  were  filled  with  colloid  mate- 
rial. The  hypophysis  was  hypertrophied,  it  weighed  0.7  gram,  its  acini  were 
distended  by  colloid  masses  with  uncommonly  numerous  eosinophile  cells  in 
the  interacinous  tissue.  Wells  remarks  quite  properly  that  if  these  changes 
could  be  determined  constantly  in  scleroderma  the  fact  would  greatly  favor  a 
thyreogenous  origin  of  this  disease. 

Actuated  by  the  same  reasons  as  in  the  therapy  of  obesity  and  psoriasis, 
etc.,  physicians  have  used  thyreoid  preparations  in  mental  disease,  in  tetanus, 
chorea  and  progressive  myopathy.  Favorable  results  in  isolated  cases  have 
even  heen  reported,  pa rt icii la rly  by  Bruce  from  the  Royal  Edinburgh  Asylum, 
by  Mahon  and  Babcock  from  the  St.  Lawrence  Eospital,  and  by  Reinhold, 
Levy-Dorn,  Grottstein,  and  Bramwell  in  tetanus,  etc.:  but  invariable  and  con- 
vincing results  have  been  obtained  more  rarely  in  these  affections  than  in  the 
diseases  previously  mentioned.  Gauthier,  Quenu,  Reclus,  Ferria  and  others 
have  employed  thyreoid  treatment  also  in  fractures  with  delayed  union  of 
hone-,  on  account  of  the  fact  that  the  thyreoid  gland  has  ;)  predominant  influ- 
ence upon  the  growth  of  hone;  the  results  were  apparently  mos!  gratifying, 
and  the  same  reason  led  t<>  the  employment  of  tin-  remedial  agenl  in  rachitis. 
Bui  here  the  watchword  for  the  present  musl  be:  temporize!  Confirma- 
tions are  wanting:  and  from  this  it  may  be  concluded  that  the  treatment  has 
been  tried  by  other-,  hilt   without  sue© 

We  cannot  close  this  discussion  without  referring  briefly  to  an  organ 
apparently  in  close  connection  with  the  functions  of  the  thyreoid  gland,  and 
by  embryologic  and  anatomic  analogic-  also  histogenetically  parallel  with  it. 
This  Is  the  hypophysis,  the  pituitary  body,  the  anterior  glandular  part  of 

which  i-  developed,  like  the  thyreoid,  from  th itoderm,  a  diverticulum  of 

the  posterior  pharyngeal  wall,  the  structure  of  which  also  consists  of  acini 

which  unite  and    form    follicles  containing  more  or  less  of  a  colloid  sub-lance. 

Unquestionably  this  gland  ha-  some  relation  to  osseous  growth,  for  it  is 
almo-i  invariably  enlarged  in  acromegalia  and  giant  <ir<>irlh.     In  isolated  i 

it   has  I n    known   to  attain  the  size  of  n   hen'-  egg,  and   the  sella   turcica   is 

abnormally  developed.      Nevertheless,  this  doe-  qoI   vet   prove,  a-  mo-t   authors 

too  hastily  assume,  that  the  hypertrophy  of  the  -land  is  the  cause  of  these 


196  MYXEDEMA 

anomalies  of  growth.  It  may  be  a  mere  coincidence,  or  vice  versa,  a  resulting 
condition  of  disease  of  the  bone,  to  a  certain  extent  a  reflex  from  the  bone  to 
the  gland.  After  thyreoidectomy  in  animals  the  hypophysis  is  said  to  hyper- 
trophy vicariously  (Hoffmeister),  and  in  a  few  cases  of  myxedema  hyper- 
trophy of  the  pituitary  gland  has  been  found.  But  Ponfick,  to  whom  we 
owe  two  very  accurately  investigated  cases  of  myxedema  recently  reported, 
found  upon  transverse  section  in  one  case  the  glandular  portion  of  the  hypoph- 
ysis enlarged,  in  the  other  case  a  decided  destruction  of  the  organ  so  that 
the  tubules  of  the  gland  were  replaced  to  a  great  extent  by  a  "  worthless  fibrous 
mass."  Here  also  there  are  evidently  contradictions  and  enigmas  which  still 
await  solution,  especially  as  we  can  state  nothing  definite  in  regard  to  possible 
therapeutic  results. 

Although  we  are  completely  in  the  dark  in  regard  to  these  last-named 
affections,  and  for  the  present  are  compelled  to  await  further  investigations, 
this  much  is  certain,  that  in  thyreoid  therapy  we  possess  a  remedy  previously 
unknown  with  which  to  combat  a  number  of  chronic  diseases,  which  even  a 
short  time  ago  were  looked  upon  as  incurable,  and  which  it  was  thought  impos- 
sible to  influence  therapeutically.  This  type  of  therapy  has  been  designated 
organotherapy  or  opotherapy,  o7ros,  juice),  and,  by  a  hasty  generalization,  the 
principles  which  are  the  foundation  of  thyreoid  gland  therapy  have  been  mis- 
applied to  preparations  from  other  organs.  It  has  been  forgotten  that,  in  the 
case  of  the  thyreoid  gland,  we  are  dealing  with  successes  gained  in  conformity 
with  well-founded  physiologic  and  pathologic  experiments  and  observations. 
If  now  we  attempt  to  extend  this  substitutiontherapy  to  all  the  other  organs 
which  are  looked  upon  (more  or  less  correctly)  as  the  cause  and  seat  of  cer- 
tain diseases,  corresponding  extracts  and  preparations  from  these  organs  are 
thrown  upon  the  market.  But  it  must  be  remembered  that,  barring  isolated 
exceptions,  there  is  no  reasonable  foundation  for  any  hope  of  success.  Here 
the  wish  has  been  father  to  the  thought,  and  views  have  sometimes  become  so 
extravagant  that  a  certain  resemblance  to  the  notorious  "  similia  similibus  " 
of  homeopathy  resulted.  As  a  matter  of  fact,  treatment  by  organotherapy  is 
by  no  means  of  recent  origin,  as  is  commonly  supposed. 

Park,  in  a  very  interesting  article  in  the  Buffalo  Medical  Journal,  1899, 
has  shown  that  it  may  be  traced  to  a  very  early  epoch  in  the  history  of  medicine. 
In  China,  since  remote  antiquity,  the  juice  from  macerated  pigs'  lungs 
is  said  to  have  been  an  efficient  remedy  for  pulmonary  diseases ;  for  headache, 
pigs'  brains  are  taken;  for  dysentery  and  chronic  diarrhea,  pigs'  intestines 
are  administered ;  semen  is  reputed  a  potent  tonic  in  chlorosis,  anemia,  impo- 
tence, etc.     Tout  comme  chez  nous! 

Strictly  speaking,  the  administration  of  ovarian  extract  is  the  only  one 
of  these  attempts  that  is  founded  upon  experimental  proof  as  well  as  upon 
analogy.  The  administration  of  pancreatic  substance  in  diabetes  (on  account 
of  the  experimentally  proven  relation  of  the  pancreas  to  glycosuria  and  dia- 
betes, is  a  therapeutic  experiment  which,  critically  examined,  is  based 
upon  nothing  more  than  analogy,  and  lacks  direct  experimental  proof.  Ee- 
garding  ovarian  therapy,  i.  e.,  the  use  of  so-called  oöphorin  tablets,  Loewy 
and  Richter  have  demonstrated  experimentally  the  interesting  fact  that  in 


THERAPY  197 

castrated  bitches  the  consumption  of  oxygen  falls  about  20  per  cent.,  the  total 
metabolism  of  gases  about  9  per  cent,  below  normal,  and  that  this  alteration 
of  respiratory  metabolism  continues  for  a  long  time  after  ovariotomy,  even 
from  six  to  twelve  months.  If  such  animals  are  fed  with  dried  ovaries,  the 
interchange  of  gase-  returns  to  its  former  height  and  even  beyond  it. 

On  the  other  hand,  under  the  influence  of  oöphorin.  no  increased  destruc- 
tion of  ^-containing  substances  takes  place — no  interchange  more  rapid  than 
in  normal  animals — nor  could  similar  results  be  obtained  after  ovariotomy  in 
animals  by  the  use  of  didymin  or  spermin.  This  explains  Landau's  success  - 
with  the  administration  of  ovarian  tablets  in  menstrual  anomalies,  during  the 
climacterium,  in  chlorosis  and  hysterical  conditions;  these  good  results  I  can 
partially  confirm  from  my  own  experience. 

Other  organic  extract.-  and  preparations  are  also  known  to  produce  certain 
effects  upon  the  organism.  Thus  adrenal  extract  increases  blood  pressure, 
preparation-  made  from  the  spleen  and  liver  have  an  influence  upon  leukocy- 
tosis, etc.  However,  these  arc  as  far  a-  can  at  present  be  ascertained,  only  local 
«•fleets  limited  to  definite  circumscribed  areas,  and  may  be  compared  to  the 
action  of  digitalis  upon  the  heart,  or  of  atropin  upon  the  pupil.  We  cannot 
claim  for  them  any  specific  curative  effect. 

The  successes  reported  with  cerebrin  in  cerebral  affections,  with  medullin 
in  diseases  of  the  hone,  with  didymin,  with  the  extract  or  with  the  substance 
of  the  adrenal^  in  Addison's  disease,  with  pancreatic  tablets  in  diabetes,  etc., 
musl  he  regarded  as  very  exceptional,  if  indeed  we  credit  them  at  all.  These 
preparations  have  not  as  yet  found  general  acceptance.  Consequently,  T  do  not 
intend  to  relate  in  detail  what  has  been  accomplished,  or,  better,  what  has 
been  attempted  by  their  use. 

In  tlii-  held  of  therapy  the  same  phenomenon  is  met  with  which  we  find 
at  present  in  other  realms  of  therapy:  professional  activity  ami  choice  are 
influenced  more  than  is  desirable  from  a  source  outside  of  (he  profession.  I 
mean  by  the  manufacturing  chemist.  The  chemical  laboratories,  especially 
of  the  anilin  works,  have  lately  thrown  themselves  zealously  into  the  endeavor. 
laudable  in  itself,  to  produce  or  to  combine  chemical  bodies  whenever  a  the- 
oretic consideration  or.  more  rarely,  an  animal  experiment  appealed  to  show 
the  existence  of  a  pharmacodynamic  property.  These  endeavor-  have  flooded 
the  medical  market  with  an  endless  number  of  new  preparation-  that  are 
distributed  for  trial,  and  with  the  hope  id'  a  successful  trial,  to  competent   and 

incompetent  judge-.  Now  then'  [g  absolutely  no  curative  agent,  no  matter 
how  slight  the  foundation  for  its  u-e.  that  doe-  not  have  its  linn  believer,  and 
serve  for  purposes  of  investigation.  Frequently  it  is  tested  in  only  a  few  cases 
from  private  practice,  and  then  its  epithon  ornans  "clinical  observation*5  is 

attached.  The  results,  in  the  form  of  reprints,  are  then  -cut  by  the  labora- 
tory into  the  world  by  thousands,  unfortunately  the  opinions  expressed  in 
these  reprint-  often  depend  upon  autosuggestion  or  an  uncritical  spirit  in 
the  author:  in  other  cases  the  effects  produced  by  the  new  preparations  are 
nowise  better  than  the  action  of  old  ami  reliable  remedies. 

Who   know-  the   preparation-!'      Their   name   i-    Legion;    they   are   sent    out 

with  *;  first-class  recommendations  "—this  commercial  expression  is  excusable 


198  ;  MYXEDEMA 

for,  in  fact,  it  is  in  place  here — are  put  upon  the  market,  and,  after  a  brief 
and  ephemeral  existence,  are  relegated  to  the  orcus  of  the  medicine  closet, 
never  to  see  again  the  light  of  day ! 

The  natural  reaction  is  a  constantly  increasing  doubt  in  regard  to  new 
remedies.  The  fascinating  reprints,  of  which  every  physician  has  a  plentiful 
supply,  owing  to  the  activity  of  the  manufacturer,  are  read  or  not  read,  but 
are  followed  very  cautiously,  for,  otherwise,  time  and  money  would  often  be 
uselessly  spent,  even  if  other  and  greater  injury  to  the  patient  does  not  result 
from  their  use. 

Why  do  I  mention  all  this  ? 

Certainly  not  to  check  a  spirit  of  rivalry  in  the  production,  nor  in  the 
testing  of  new  remedies  by  competent  physicians,  and  this  I  desire  to  repeat 
with  emphasis  and  to  bring  out  prominently.  The  advantage  which  lias 
already  resulted  from  organotherapy  is  so  obvious  that  many  a  failure  would 
be  amply  compensated,  for — but  I  must  advise  those  who  busy  themselves  with 
this  line  of  investigation  to  be  more  cautious  in  arriving  at  conclusions,  and 
to  exercise  more  patience  in  collecting  and  more  care  in  utilizing  their 
material. 

It  is  not  wise  to  cut  the  corn  while  it  is  yet  green;  harvesting  also  is  an 
art.  Whoever  has  not  learned  this,  whoever  works  in  a  field  which  is  too 
narrow,  i.  e.,  in  other  words,  whoever  lacks  the  necessary  experience  and  the 
endowment  of  a  faculty  for  scientific  criticism,  should  refrain  from  giving 
opinions  on  such  a  subject. 

To  this  group  of  over-hasty,  uncritical,  and,  therefore,  untrustworthy  pub- 
lications, belong  those  chateaux  en  Espagne  which  form  the  greater  part  of 
that  "  so-called  "  organotherapeutics  with  which  we  have  been  favored  in  the 
last  few  years.  With  alarming  haste  the  manufacturing  chemists  have  made 
preparations  from  all  of  the  organs,  and  offered  them  to  the  medical  profes- 
sion for  its  kind  consideration. 


ADDISON'S     DISEASE 

Bv    L.    REISS,    Berlin 

In  recent  pathological  discussions  attempts  have  been  made  to  refer  the 
clinical  symptoms  in  a  number  of  general  affections  to  a  so-called  "■'auto- 
intoxication" produced  by  the  decrease  or  absence  of  the  "internal  secretion" 
of  an  important  organ  of  the  body.  Of  course  this  view  refers  chiefly  to  those 
forms  of  disease  in  which  clinical  and  pathologico-anatomical  experience 
have  taught  us  to  recognize  the  invariable  predominance  of  changes  in  an 
organ  having  a  -ecretory  character.  An  example  which  host  illustrates  this  is 
the  wonderful  Bymptom-picture  of  myxedema,  the  direct  dependence  of  which 
upon  a  cessation  or  absence  of  function  of  the  thyreoid  gland  has  been  lately 
proven  with  all  the  certainly  that  can  ho  desired. 

To  the  general  diseases,  in  which,  at  the  first  glance,  it  must  he  ohvious 
that  similar  functional  disturbances  are  causative,  belongs  also  the  remarkable 
Bymptom-group  which,  about  the  middle  of  the  last  century,  was  first  accu- 
rately described  by  the  English  physician,  Addison,  and  to  which,  therefore, 
his  name  ha-  been  attached.  The  relation  of  this  clinical  picture  to  a  well- 
defined  disease  of  the  adrenal  bodies  which  is  preseni  in  the  majority  of  cases 
ha-  governed  the  views  of  observers  from  remote  tune-  regarding  the  nature 
of  the  disease,  and  in  spite  of  the  many  differences  of  opinion  which  have 
become  prominenl  in  the  Lasl  decade-  regarding  the  pathogenesis  of  Addison's 
disease j  the  greal  majority  of  physicians  maintain  that  a  cessation  of  Ihe 
function  of  Ihr  minimis  i-  the  essentia]  basis  of  the  affection.  It  i<  also  in 
harmony  with  this  view  that  lately,  by  a  transference  of  the  practical  question 
of  the  treatment  of  this  affection  by  organotherapy,  favorable  expectations 
have  been  aroused  so  that  many  trials  bave  already  been  made  of  this 
met  bod. 

Bui  nevertheless,  upon  closer  observation,  the  conditions  do  not  appear  so 

simple.  Many  of  the  clinical  symptoms  cannot  ho  referred  without  further 
consideration  to  a  disturbed  function  of  the  adrenals-  a  constanl  group  of 
clinical  ami  anatomical  findings  cannot  he  said  to  have  been  found,  and  thus 
an  accurate  weighing  of  the  experiences  gathered  up  to  this  time  lead-  to  the 
conclusion  that  the  exclusive  dependence  of  Addison's  disease  upon  disease 
of  the  adrenal-,  although  in  mam  respects  quite  likely,  ha-  not  been  absolutely 
proven,  and  doc-  not  BuflSce  fully  to  explain  the  pathogenesis  of  the  disease. 

I'ndcr  these  circumstances,  it  is  instructive  to  investigate  the  mosl  impor- 
tant point-  and  ascertain  whether  <>r  mil  Ihr  weight  <>f  evidence  points  in 
a  dirrct  dependence  »/"'»  disease  of  Ihr  suprarenal  ho, His.     In  the  following 

100 


200  ADDISON  S   DISEASE 

survey  of  the  present  status  of  our  knowledge  of  the  pathology  of  the  affection, 
this  problem  is  our  chief  interest.  We  hope  clearly  to  demonstrate  what  the 
investigations  of  the  last  half  century  have  contributed  in  explanation  of 
the  disease,  and  what  is  left  for  future  studies  to  elucidate. 

A  brief  description  of  the  clinical  picture  must  precede  the  rest  of  my 
discussion. 

CLINICAL   PICTURE    OF   ADDISON'S   DISEASE 

The  description  need  be  but  very  brief  for,  in  the  portrayal  of  the  clinical 
symptoms,  the  first  description  given  by  Addison  in  1855  is  practically  ex- 
haustive, and  many  of  the  later  observations  have  but  supplemented  this  in 
certain  respects. 

All  typical  cases  of  the  disease  show  (simultaneously  or  serially)  the  fol- 
lowing four  groups  of  symptoms : 

1.  General  adynamia;  2.  gastric  and  i?itcstinal  disturbances;  3.  general 
nervous  symptoms;  4.  abnormal  pigmentation  of  the  surface  of  the  body. 

I  here  emphasize  the  conception  of  "  typical  cases,"  and  do  not  believe  it 
advisable  in  describing  the  nature  of  the  disease  to  deviate  too  far  from  this 
conception.  In  particular,  I  do  not  believe  that  we  ought  to  include  as  cases 
of  Addison's  disease  (as  has  often  been  done  of  late)  those  in  which  the  most 
conspicuous  symptom,  the  abnormal  pigmentation  of  the  skin,  is  absent,  even 
though  examples  of  this  kind  (of  which  more  will  be  mentioned  later  on) 
may  be  important  in  the  explanation  of  the  nature  and  the  pathogenesis  of 
the  disease.  The  differentiation  of  characteristic  symptom-pictures  can 
advance  our  clinical  knowledge  only  when  it  is  carried  out  with  the  neces- 
sary consistency. 

The  signs  of  adynamia  as  a  rule  develop  very  insidiously,  showing  them- 
selves in  general  malaise  with  exhaustion  upon  slight  exertion,  gradually 
increasing  to  extreme  muscular  weakness,  particularly  of  the  lower  extrem- 
ities, so  that  walking  may  become  very  difficult.  These  symptoms  cannot  well 
be  referred  to  a  profound  disturbance  of  nutrition  of  the  muscles,  for,  as  a 
rule,  neither  ver}>-  marked  emaciation  nor  muscular  atrophy  is  present,  at  least 
in  the  early  stages  of  the  disease.  A  weakened  condition  of  the  heart  muscle 
is  also  apparent,  particularly  in  advanced  stages  of  the  disease.  The  pulse 
is  often  very  small,  and,  at  least  in  the  earlier  stages,  more  often  slowed  than 
accelerated.  Subnormal  temperature  (95°  F.  or  a  little  above  this)  has  been 
repeatedly  observed,  particularly  in  the  terminal  stages  of  the  disease. 

The  muscular  weakness  cannot  be  attributed  to  a  marked  anemia,  for  the 
microscopic  examination  of  the  blood  (which  will  be  referred  to  more  in 
detail  later)  has  generally  indicated  even  in  a  late  stage  of  the  disease  only 
a  moderate  diminution  of  the  red  blood-corpuscles  and  leukocytosis  while 
some  recent  observations  have  shown  a  conspicuously  large  number  of  eryth- 
rocytes. 

The  disturbances  referred  to  the  digestive  canal  show  themselves  in  the 
earlier  stages  of  the  affection  by  general  dyspeptic  complaints:  Loss  of  appe- 
tite (often  extreme),  occasionally  bulimia;  tendency  to  nausea  and  vomiting, 
sense  of  pressure  in  the  epigastrium;  also  disturbance  of  intestinal  activity 


CLINICAL  PICTURE  OF  ADDISON'S  DISEASE  201 

which  more  frequently  leads  to  diarrhea  than  to  constipation.  With  this 
very  often,  even  early,  there  are  marked  pains  in  the  abdomen  especially  in 
the  epigastrium,  in  both  lumbar  regions,  and  in  the  right  and  left  hypochon- 
drium.  intermittent  at  first,  subsequently  often  becoming  continuous.  All  of 
these  symptoius  increase  late  in  the  course  of  the  disease,  and  often  become 
so  severe  that  after  a  time  the  gastrointestinal  disturbances,  with  stubborn 
vomiting  and  often  steady  diarrhea,  rapidly  decrease  the  strength. 

The  symptoms  which  may  be  referred  to  the  nervous  system  are  slight  at 
the  onset  of  the  disease,  of  a  general  character,  and  limited  for  the  most  part 
to  psychical  apathy,  tendency  to  headache  and  the  like.  Later,  attacks  of 
vertigo  and  syncope  are  usually  observed,  not  infrequently  also  epileptiform 
attacks  and  somnolence.  Death  occurs  most  often  after  coma  and  convulsive 
phenomena. 

'Flic  most  conspicuous  Bymptom  of  the  disease  in  all  well  marked  cases  is 
the  discoloration  of  the  skin  which  has  given  the  affection  the  designation 
of  "  bronze  disease/'  Like  the  other  symptoms,  this  usually  develops  gradually 
from  a  Lighl  yellowish  brown  up  to  a  dark  brownish  black  (mulatto  color, 
uegro  color).  It  often  begins  simultaneously  with  the  general  asthenia,  but 
may  precede  this,  in  some  cases  even  by  a  long  time  (in  one  recorded  ease 
twelve  years).  The  bronzing  appears  most  often  on  the  places  which  are 
exposed  to  the  air  (face,  neck,  hands),  and  ou  those  which  normally  show 
mo-t  pigmentation  (the  axillae,  the  areola  of  the  nipple,  the  Linea  alba,  the 
genital  region),  and  thence  distributes  itself  over  the  reel  of  the  skin.  Upon 
the  uniformly  pigmented  surface  there  often  develop  later  circumscribed,  still 
darker  area- ;  in  some  cases,  on  the  other  hand,  we  find  zones  which  are  without 
pigment  (leukoderma ). 

The  simultaneous  involvement  of  certain  mucous  membranes  in  this  pig- 
mentation has  yyy  properly  been  emphasized  throughout  the  literature  of 
Addison's  disease  as  especially  important  in  the  differential  diagnosis  from 
other  discoloration^  of  the  skin.  Almost  invariably  the  muri, us  membrant  of 
the  mouth  is  affected,  usually  in  the  form  of  irregular  bluish  black  spots, 
their  Beat  being  chiefly  upon  the  mucous  membrane  of  the  Lips  and  palate. 
According  to  my  experience,  the  tongue  i\>-^'v\r~.  more  attention  than  is  usually 
given  to  it.  In  the  cases  seen  by  me  it  often  Bhows  in  different  areas  a  very 
conspicuous  inky  stain.  Sometimes  pigment  areas  are  found  upon  the  vaginal 
mucous  membrane;  exceptionally  also  upon  the  conjunctiva  palpebrarum  and 

sclera'  and  upon  the  VOCal  cords. 

The  pigmentation,  as  a  rule,  gradually  increases  in  intensity  throughout 
the  course  of  the  disease.  Only  exceptionally  has  a  diminution  been  noted 
prior  t"  death.     Somewhat  more  often  transitory  remissions  of  the  bronzing 

have  l n  reported.     I  myself  have  Been  in  two  cases  a  bleaching  of  the  skin 

Lasting  several  months  (with  a  simultaneous  general  improvement)  and  later 
increased  discoloration. 

The  course  of  the  Bymptoms  just  mentioned  is  decidedly  chronic;  only 
exceptionally  i-  the  onsel  acut.'  and  progress  rapid.  The  Beverer  symptoms 
follow  tin'  milder:  not  infrequently  tiny  come  on  Borne  months  or  weeks  prior 
to  death,  with  a  certain  Buddenness.     Two  years  may  be  mentioned  a-  the 


202  ADDISON'S  DISEASE 

average  duration  of  the  disease,  as  determined  from  a  large  collection  of 
cases.  The  termination  is  always  fatal;  in  the  few  cases  which  have  been 
described  as  cured  the  diagnosis  is  doubtful. 

To  complete  the  description  it  may  be  stated  that  Addison's  disease  (par- 
ticularly in  North  Germany)  is  quite  rare,  that  with  the  exception  of  earliest 
childhood  and  extreme  old  age  it  attacks  all  periods  of  life  quite  uniformly, 
and  is  more  frequent  in  men  (60  to  70  per  cent.)  than  in  women.  Important 
etiologic  factors  cannot  be  determined ;  in  a  number  of  cases  prolonged  psychi- 
cal depression  (care  and  sorrow)  appear  to  play  a  role. 

Besides  those  diseases  with  which  the  malady  is  often  associated  (tubercu- 
losis, and,  to  a  lesser  extent,  carcinosis)  I  must  mention  certain  cutaneous 
complications  which  have  become  known  by  experience,  among  which  are 
especially  scleroderma,  and  in  rarer  cases  prurigo,  mycosis  fungoides,  etc. 

GROSSER  PATHOLOGICO-ANATOMICAL  LESIONS  IN  ADDISON'S 

DISEASE 

As  regards  the  pathological  anatomy  of  the  disease  numerous  investigations 
in  the  last  few  decades  have  confirmed  the  findings  emphasized  by  Addison, 
i.  e.,  the  coincidence  of  the  symptom-complex  just  described,  with  disease  of 
the  suprarenal  bodies.  In  the  overwhelming  majority  of  the  recorded  cases, 
a  profound  change  in  these  organs  with  destruction  of  the  greater  part  of  the 
normal  parenchyma  has  been  observed.  Furthermore,  experience  has  shown 
that  Addison's  disease  is  not  produced  by  any  and  all  the  pathological  changes 
of  the  adrenals  but  that  a  definite  form  of  disease  of  the  organ  is  usually 
present,  particularly  a  form  of  chronic  tuberculosis,  in  which  the  parenchyma 
is  rapidly  destroyed,  partly  by  caseous  degeneration,  partly  by  fibrinous  con- 
traction. The  macroscopic  changes  according  to  age  and  distribution :  In  f he 
majority  of  cases  the  adrenals  are  enlarged  (occasionally  to  several  times  the 
normal) ;  upon  section  the  tissue  in  part  shows  inflammatory  swelling  with 
foci  of  caseous  softening;  in  other  areas,  contraction  and  induration  with 
hard,  cheesy,  or  calcified  deposits.  In  a  small  number  of  cases  processes  of 
contraction  are  predominant,  so  that  the  organ  is  smaller,  occasionally  so 
small  that  it  can  only  be  found  with  difficulty.  The  disease  of  the  suprarenal 
bodies  in  the  majority  of  cases  is  bilateral  but,  as  a  rule,  not  equally  developed 
on  the  two  sides.  In  the  interior  of  the  individual  organ  the  cortical  and 
the  medullary  substance  are  as  a  rule  uniformly  implicated,  so  far  as  can  be 
noted  at  the  autopsy.  Tubercle  bacilli  have  lately  been  found  by  many 
observers  in  the  foci  of  disease. 

In  a  small  number  of  cases  the  adrenals  show  other  forms  of  disease. 
Among  these,  according  to  the  latest  investigations  and  reports,  comparatively 
the  most  frequent  seems  to  be  simple  atrophy  of  the  organ,  a  change  which 
in  some  instances  is  so  extreme  that  the  adrenal  appears  to  be  absent.  But 
it  is  very  likely  that  some  of  these  atrophic  cases  represent  only  the  remains  of 
inflammatory  processes  after  the  absorption  of  softened  foci.  In  a  still  smaller 
number  of  cases  malignant  neoplasms  (carcinoma  and  sarcoma)  have  been 
found  in  the  parenchyma  of  the  organ.     Still  more  rarely  other  diseases,  such 


GROSSER  PATHOLOGICO-AXATOMICAL  LESIONS  203 

as  amyloid  degeneration,  gummatous  changes,  echinococcus  disease,  etc.,  occur. 
Finally,  destruction  of  the  organ  by  hemorrhage  has  been  occasionally  men- 
tioned (in  cases  running  an  acute  course). 

An  important  point  is  that  in  a  large  number  of  the  accurately  investigated 
cases  the  neighborhood  of  the  adrenals  has  also  been  found  changed,  so  that 
as  a  result  of  adhesions  and  abnormal  connective  tissue  changes  (apparently 
the  remains  of  circumscribed  peritonitis)  the  adrenals  have  coalesced  and 
become  embedded  in  the  neighboring  parts.  Among  the  areas  thereby  affected 
the  filaments  and  plexuses  of  the  abdominal  sympathetic  (above  all,  of  the 
solar  plexus  and  of  the  celiac  ganglia  which  are  situated  in  the  neighborhood 
of  the  suprarenals)  have  quite  often  been  found  embedded  in  thick  masses 
of  connective  tissue. 

In  the  purest  eases  the  changes  to  be  found  in  the  adrenals  and  in  their 
immediate  surroundings  are  the  only  abnormal  autopsy  findings.  Frequently, 
however,  other  changes  take  place,  among  them  (naturally  and  primarily) 
tuberculous  lesions  which  attack  the  lungs  in  about  one-third  of  the  ca 
But  Addison's  disease  does  not  often  complicate  cases  of  advanced  phthisis. 
Similarly  malignant  neoplasms  of  the  adrenals  may  exist  alone  or  be  com- 
bined with  tumors  of  other  abdominal  organ-. 

So  far  I  have  purposely  considered  only  the  simple  typical  cases  of  the 
disease.  This  method  I  should  like  to  continue  for  the  present,  excluding 
the  cases  above  referred  to,  which  present  the  clinical  picture  of  Addison's 
disease  bul    -how  no  changes  of  the  adrenals.     The  question   must   now  be 

ed  :  May  we,  and  must  we,  in  such  pure  cases  with  a  typical  symptom- 
picture  and  well-developed  disease  or  destruction  of  the  adrenals,  refer  the 
former  directly  to  the  latter? 

Before  deciding  (his  question,  two  other  questions,  it  appear-  to  me,  must 
fu-.-t  be  solved  :  |  1  )  May  the  main  symptoms  of  Addison's  disease  he  produced 
by  certain  general  conditions  which  are  present  in  Ihr  affectionf  and  (2)  Can 
we  believe  with  our  present  knowledge  id'  the  nature  and  function  of  ihr 
adrenals  that  disease  of  these  may  produce  the  symptoms  of  Addison's  disease? 

In  regard  to  the  first  question  a  number  of  maladies  niu-t  he  considered 
in  which,  a-  a  rc-uli  of  a  profound  anemia  and  cachexia,  with  the  general 
symptoms  of  asthenia  (and  eventually  also  gastric  and  nervous  disturbances), 
an  abnormal  pigmentation  of  the  -kin  may  develop.  To  ibis  group  belong 
certain  cases  of  malarial  cachexia,  pseudo-leukemia,  pellagra  (Neusser),  the 
so-called  vagrant's  disease  which  is  produced  by  deprivation  of  all  kind-. 
advanced  stages  of  tuberculosis  and  carcinosis,  and  others.  But  it  is  not 
likely  that  any  di-ea-e  of  the  adrenals  exists  in  the-,,  disorders.  Moreover, 
the  discoloration  of  the  -kin  differs  in  these  cases  mosl  distinctly  from  that 
seen  in  Addison's  di-ea-e.  In  the  diseases  ju-l  mentioned  it  i-  usually  of 
slighter  degree  than  in  Addison's  disease,  and  is  far  less  generally  distributed; 
it  rarely  shows,  a-  in  the  latter  malady,  the  formation  of  dark  areas  on  ;i 
background  of  diffusely  discolored  skin,  and  above  all  the  accompanying 
pigmentation  of  the  mucous  membranes  ;-  absent.  On  the  other  hand,  in 
the  general  diseases  enumerated  above  the  principal  pathogenic  factor  i-  a 


204  ADDISON'S  DISEASE 

disturbance  in  nutrition  and  a  change  in  the  composition  of  the  blood,  which 
is  generally  absent  in  Addison's  disease:  The  anemia,  as  a  rule,  is  only  devel- 
oped to  a  moderate  degree  in  Addison's  disease;  the  red  blood  count,  even 
in  advanced  stages,  is  rarely  below  3,000,000;  the  hemoglobin  also  has  been 
often  found  comparatively  high.  The  increase  of  the  erythrocytes,  which  has 
been  lately  determined,  is  not  constant  and  is  still  unexplained ;  in  one  case 
from  6,800,000  to  7,200,000  were  found,  and,  shortly  before  death,  6,500,000. 
The  frequently  accompanying  leukocytosis,  with  the  relative  increase  of 
lymphocytes  which  has  been  recently  reported,  was  not  marked  enough  to 
constitute  a  characteristic  change  in  the  blood  composition.  The  pigmenta- 
tion seen  in  tuberculosis  is  not  of  importance,  inasmuch  as  changes  resembling 
Addison's  disease  occur  only  in  its  late  stages;  typical  cases  of  Addison's 
disease,  however,  are  rarely  the  accompaniments  of  advanced  stages  of  tuber- 
culosis. 

In  answer  to  the  other  question,  what  consequences  are,  a  priori,  to  be 
expected  upon  destruction  of  the  adrenals,  it  is  necessary  to  briefly  review 
the  reports  concerning  the  anatomy  and  physiology  of  these  organs. 

ANATOMY  AND  PHYSIOLOGY  OF  THE  ADRENALS  . 

Formerly  the  adrenal  was  assumed  to  be  essentially  a  part  of  the  nervous 
system,  and  its  medullary  substance  was  described  as  consisting  almost  exclu- 
sively of  ganglion  cells.  But  the  newer  histologic  investigations  are  unanimous 
in  this,  that  the  cortical  substance  as  well  as  the  medullary  substance  contains 
chiefly  parenchyma  cells  which  show  a  varying  size  and  form  in  different  areas, 
are  arranged  in  groups  inside  of  a  connective  tissue  structure,  and  contain 
very  abundant  pigment,  chiefly  in  the  intermediary  zone  (Virchow).  The 
rich  blood  supply  of  the  organs  has  long  been  emphasized ;  this  is  shown  partly 
by  the  comparatively  great  number  of  afferent  and  efferent  large  vessel  trunks, 
and  partly  by  the  very  dense  capillary  network  (particularly  in  the  medullary 
substance).  The  parenchyma  cells  are  everywhere  in  intimate  relation  with 
the  walls  of  the  capillaries,  according  to  some  reports  in  part  directly  within 
them.  Between  the  cells,  excreted  "  colloid  "  masses  have  of  late  been  fre- 
quently observed  (Auld).  All  authors,  even  the  most  recent,  agree  that  the 
organs  (especially  their  medullary  substance)  are  particularly  rich  in  nerve 
elements,  i.  e.,  in  non-medullated  (sympathetic)  and  medullated  nerve  fibers 
as  well  as  also  in  ganglion  cells  deposited  in  the  parenchyma.  Numerous 
nerves  unite  the  organs  with  the  neighboring  parts  of  the  nervous  system, 
particularly  with  the  semilunar  ganglion  and  the  other  parts  of  the  solar 
plexus;  they  have  even  been  followed  further,  and  traced  into  the  splanchnic 
nerve,  the  vagus  and  the  phrenic  nerve.  Some  authors  have  described  small 
ganglion  cell  groups  situated  upon  the  external  part  of  the  capsule  of  the 
adrenal. 

The  conception  of  the  embryologic  development  of  the  adrenals  differs 
with  various  investigators;  the  majority  of  observers  believe  that  there  is 
an  intimate  relation  between  the  medullary  substance  (which  develops  sepa- 
rately from  the  cortex)  and  the  (sympathetic)  nervous  system,  either  assum- 


GROSSER  PATHOLOGICO-ANATOMICAL   LESIONS  205 

ing  a  direct  development  of  the  adrenal  medullary  substance  from  the  ganglion 
of  the  sympathetic,  or  a  later  growth  from  the  .sympathetic  ganglion  cells  and 
nerve  fibers. 

In  spite  of  many  points  which  are  still  obscure  the  complicated  anatomical 
structure  of  the  adrenals  gives  us  the  impression  that  they  are  (ductless) 
secretory  organs,  constructed  with  a  comprehensive  innervation  apparatus. 

Still  more  complicated,  and  in  many  respects  uncertain,  is  our  knowledge 
of  the  physiologic  function  of  the  adrenals. 

For  a  long  time  they  have  been  classed  with  the  well  known  glandular 
ductless  organs,  being  designated  as  blood-vessel  glands  serving  an  unknown 
purpose.  Particular  attention  was  drawn  to  the  adrenals  by  the  first  descrip- 
tions of  the  Addison  symptom-complex,  and  this  caused  a  deeper  scientific 
interest  regarding  their  importance,  and  the  investigation  of  their  function. 
And  thus,  soon  after  the  publication  of  Addison's  views,  a  series  of  experi- 
mental researches  were  began  which  had  for  their  purpose  the  extirpation  of 
the  adrenals  in  animals,  and  the  observation  of  symptoms  thus  produced,  in 
order  to  determine  the  functional  importance  of  these  organs. 

But  the  difficulty  of  such  investigations  was  soon  shown  in  the  uncertainty 
of  the  results.  This  gave  rise  to  the  important  question,  whether  the  adrenals 
were  to  be  looked  upon  as  organs  necessary  to  life.  This  question  was  an- 
swered definitely  in  the  affirmative  by  the  first  investigator.  Brown- Sequard; 
in  a  publication  in  1856  he  stated  that  after  removal  of  both  adrenals  all  the 
animals  died  in  a  short  time  (one  to  two  days)  with  prostration  and  severe 
nervous  symptoms.  Bui  his  reports  were  at  first  not  confirmed  by  other  ob- 
servers; on  the  contrary,  there  soon  appeared  a  number  of  communications 
(among  which  I  -hall  mention  only  those  of  Philippeaux,  Gratiölet,  Harley 
and  Schill'),  according  to  which  certain  animals,  in  spite  of  the  loss  of  both 
adrenals,  continued  to  live  tor  a  long  time  (several  month-),  and  from  which 
it  appeared  likely  that  the  death  of  the  experimental  animals  was  produced 
by  Lesions  of  neighboring  parts  (peritoneum,  abdominal  nerve  plexus,  etc.). 
At  this  point  I  mu-t  refer  to  a  series  of  experiments  by  Nothnagel,  who 
produced  bilateral  contusion  of  the  adrenals  in  a  great  number  of  rabbits,  a 
few  of  which  were  .-till  living  eighteen  months  later  and  showed  no  g] 
Lesions. 

Thus  the  vital  importance  of  the  adrenals  was  for  a  long  time  a  subject 
of  doubt.  P>ut  ;i  series  of  new  investigations  substantiated  the  original  opinion 
of  Brown- Sequard.  These  (conducted  by  Tizzoni,  Abelous  and  Langlois,  de 
Domenicis,  Cybulski,  Szymonowicz  and  others)  showed  that  in  a  number  of 
different  animal  -peril-  (dogs,  guinea-pigs,  frogs,  etc.)  death  invariably  re- 
sulted after  a  complete  removal  of  both  adrenals. 

The  period  before  death  varied  (according  to  the  animal  and  according 
to  certain  auxiliary  conditions)  from  a  few  hours  up  to  several  month-.  By 
careful  control  experiment-  it  was  Bhown  that  only  the  Loss  of  the  adrenals 
could  he  the  cause  of  death.  An  oppo-iie  re-nit  ha-  been  obtained  in  some 
investigations,  very  few  of  them  recent.  This  contradiction  may  he  explained 
in  various  ways:  Either  the  observation  of  ihr  animal-  may  have  been  too 
brief,  or  the  removal  of  the  adrenals  was  incomplete. 


206  ADDISON'S  DISEASE 

Finally,  as  an  explanation  of  this  problem  (as  of  many  others  to  be  men- 
tioned later)  we  must  remember  the  presence  of  the  so-called  accessory  or 
supplementary  suprarenal  bodies  to  which  Marchand  was  the  first  to  call 
attention.  These  accessory  adrenals  are  found  particularly  in  the  neighbor- 
hood of  the  internal  genitalia,  which  have  been  experimentally  proven  to  be 
capable  of  decided  hypertrophy  after  removal  of  the  adrenals.  In  conclusion 
it  has  lately  been  regarded  as  settled  that  after  complete  removal  of  the 
adrenals  a  continued  healthy  existence  is  impossible. 

More  difficult  is  the  decision  of  the  question,  what  are  the  disturbances 
of  function  in  experimental  animals  after  removal  of  the  adrenals? 

In  the  first  place  a  number  of  symptoms  in  these  animals  may  be  referred 
to  general  nutritive  disturbance  (mostly  diarrhea)  ;  further  some  observers 
have  noted  lowering  of  temperature  and  lowered  blood-pressure.  Such  symp- 
toms are  not  consequences  of  loss  of  the  function  of  the  adrenals,  as  has  lately 
been  often  affirmed.  .  On  the  contrary,  they  may  find  sufficient  explanation  in 
the  severity  of  the  operation  and  in  various  auxiliary  circumstances.  It  must 
be  emphasized,  too,  that  up  to  the  present  time,  no  animal  experiment  has  been 
successful  in  producing  unmistakably  the  principal  clinical  symptom  of  Addi- 
son's disease,  viz.,  the  pigmentation  of  the  skin. 

In  some  more  extensive  series  of  experiments  a  few  of  the  animals  lived 
for  a  longer  time  and  some  developed  areas  of  pigment  upon  the  mucous 
membrane  of  the  mouth  or  nasal  cavity;  but  it  is  doubtful  whether  in  these 
exceptional  cases  the  operation  produced  the  pigmentation. 

On  the  other  hand  more  conspicuous  symptoms  relating  to  the  nervous 
system  were  observed  in  the  experimental  animals.  In  those  that  soon  suc- 
cumbed there  were  convulsions,  symptoms  of  vertigo,  rotary  movements,  and 
the  like;  among  the  animals  which  lived  longer,  paralytic  conditions,  con- 
tractures, etc.,  developed.  More  profound  pathologico-anatomical  changes  of 
the  nervous  system  have  been  described  only  by  Tizzoni.  In  his  cases  there 
were  lesions  in  the  central  nervous  system,  particularly  the  medulla  oblongata, 
the  cervical  cord  and  cerebellum,  as  well  as  in  the  abdominal  plexus  of  the 
sympathetic,  and  certain  peripheral  nerve  trunks.  In  animals  that  died 
quickly  the  central  nervous  system  showed  hyperemia  with  hemorrhages  and 
cell  infiltration  surrounding  the  vessels ;  in  the  cases  running  a  chronic  course 
the  changes  were  more  in  the  form  of  column  degeneration  and  atrophy 
of  the  gray  substance.  The  starting  point  of  the  process  was  apparently  the 
abdominal  sympathetic.  But  nothing  analogous  to  this  has  been  reported  by 
other  experimenters. 

Brown-Sequard  believed  that  he  could  determine  important  changes  in  the 
blood  of  these  experimental  animals,  particularly  a  decided  increase  of  pigment 
with  pigment  emboli  in  the  organs.  From  this  observation  he  inferred  an 
intimate  connection  between  the  adrenals  and  pigment  formation  in  the  body. 
But  confirmation  of  these  reports  by  other  observers  is  lacking.  Reliable 
results  were  furnisbed  by  prolonged  investigations  with  the  injection  of  the 
bloo.d  of  epinephrectomized  animals  into  healthy  animals  by  Brown-Sequard 
and  by  later  observers  (particularly  Abelous,  Langlois,  etc.).  Tbese  experi- 
ments showed,  after  removal  of  the  adrenals,  a  conspicuous  toxicity  of  the 


GROSSER  PATHOLOGICO-AXATOMICAL  LESIONS  207 

blood  serum  so  that  when  it  was  injected  into  animals  one  of  whose  adrenals 
had  been  excised  death  was  produced  or  hastened.  From  the  sum  of  these 
investigations  the  observers  conclude  that,  after  the  operation,  substances  cir- 
culate in  the  blood  which  under  normal  circumstances  are  rendered  harmless 
by  the  adrenals;  that  the  latter  are  therefore  protective  organs  in  relation  to 
certain  toxic  products  of  metabolism.  Further  consideration  caused  a  number 
of  these  observers  to  emphasize  the  similarity  of  the  symptoms  to  those  of 
curare  poisoning.  This  was  true  of  the  animals  operated  upon  as  well  as 
those  animals  into  whom  the  blood  was  injected  (particularly  in  regard  to 
the  action  upon  the  nerves).  It  was  also  determined  that  after  inoculation 
of  the  blood  and  serum  of  dogs  into  other  animals  whose  muscles  were  ex- 
hausted by  tetanizing  action  was  produced  similar  to  that  after  the  removal 
of  the  adrenals.  Regarding  the  substances  which  appear  to  be  neutralized 
by  the  normal  function  of  the  adrenals,  these  experiments  justify  us  in  believ- 
ing that  they  are  the  toxic  products  of  the  metabolism  of  muscular  activity. 

Finally  I  must  mention  the  researches  of  Jacobi,  which  appear  to  prove 
an  intimate  relation  between  the  adrenals  and  intestinal  peristalsis.  And  this 
influence  must  be  looked  upon  as  an  inhibitive  action  exerted  on  the  gut  by 
the  adrenals.  Extirpation  of  the  adrenals  acted  like  division  of  the  splanchnic 
and  produced  active  intestinal  peristalsis  while  irritation  of  the  adrenal-  caused 
i  be  intestine  to  remain  quiescent.  The  adrenals  accordingly  are  looked  upon 
as  branches  of  the  splanchnic,  and  the  inhibitive  tracts  controlling  the  intes- 
tine considered  to  be  fibers  which  lead  from  the  adrenals  to  the  semilunar 
ganglions.  It  is  true  these  investigations  have  not  as  yet  been  thoroughly 
confirmed. 

In  the  reports  of  experiments  up  to  the  present  time,  therefore,  certain 
points  of  support  are  found  for  ascribing  to  the  adrenals  an  important  func- 
tion in  the  organism. 

This  conviction  is  strengthened  and  confirmed  by  other  recent  investiga- 
tions, in  which  the  attempt  was  made  to  introduce  the  active  constituents  of 
the  adrenals  in  the  form  of  an  organic  extract  (watery,  glycerin-containing, 
etc.)  into  animals  by  injection,  and  to  study  the  action  thus  produced.  I 
.-hall  only  mention  a  i'cw  of  the  most  important,  and  the  conclusions  which 
have  been  drawn  from  them  regarding  the  function  of  the  adrenals: 

After  a  few  earlier  observers  had  determined  the  toxicity  of  adrenal 
extracts,  noting  the  effect  of  injections  in  differenl  animals  who  showed 
symptoms  of  general  body  and  nervous  weakness,  Oliver  and  Schäfer  (1894 
and  1895)  were  the  firsl  to  make  minute  Btudies  regarding  this  condition. 
They  found  as  the  mosl  conspicuous  action  of  intravenous  injections  of  the 
extract  (particularly  that  obtained  from  the  medullary  substance)  a  transitory 
but  very  decided  rise  of  blood-pressure.  Further  investigations  (cutting  the 
vagus,  injection  of  atropin,  destruction  of  the  medulla  oblongata  and  of  the 

spinal  cord,  etc.)   proved  that  this  rise  in  hi l-pressure  ia  ^^^  to  a  direct 

increase  of  vascular  tonus  and  general  muscle-tone  (particularly  in  the  heart 
and  in  the  vessels).     The  extract,  besides  strengthening  the  cardiac  action, 

i    -lows    it.      Adrenal    extracts    which    were   taken    from    cases   «>f    A.ddison'8 

disease  were  inactive.    The  observers  conclude:  That  the  adrenals  Becrete  a 


208  ADDISON'S  DISEASE 

substance  which  reaches  the  blood,  and  gives  to  the  muscles  the  degree  of 
tension  necessary  for  their  functions. 

In  a  similar  manner  Cybulski  and  Szymonowicz  proved  the  rise  in  blood- 
pressure  (by  contraction  of  the  vessels)  and  the  strengthening  of  the  cardiac 
activity  resulting  from  injections  of  suprarenal  extract.  But  upon  further 
investigation  (after  severing  the  vagus  and  spinal  cord,  injecting  atropin, 
etc.)  they  obtained  results  which  appeared  to  favor,  not  a  peripheral  action 
of  the  extract,  but  an  influence  upon  the  central  nervous  system,  particularly 
the  vasomotor  centers  of  the  cord.  They  also  found  marked  irritation  of  the 
respiratory  center.  They  therefore  assume  that  the  secretion  furnished  by 
the  adrenals  to  the  blood  is  intended  to  maintain  the  tonus  of  the  cardiac, 
vasomotor  and  respiratory  centers.  But  the  majority  of  the  later  investiga- 
tions have  favored  the  assumption  of  a  peripheral  action  of  the  adrenal 
extract.  Only  v.  Cyon  believes  from  his  investigations  that  the  rise  in  blood- 
pressure  depends  for  the  most  part  upon  an  irritation  of  the  vasomotor  cen- 
ters. On  the  other  hand,  the  researches  of  Velich  favor  the  view  that  the 
vascular  contractions  which  he  observed  after  injection  of  adrenal  extract  into 
the  tongue,  conjunctiva,  ear,  intestine  and  kidneys  depend  upon  an  influence 
of  the  extract  upon  the  peripheral  yascular  apparatus  as  well  as  upon  the 
co-operation  of  spinal  vaso-constrictor  centers.  Biedl  obtained,  after  complete 
destruction  of  the  spinal  cord,  marked  rise  in  blood-pressure  by  intravenous 
injections  of  suprarenal  extract,  so  that  an  irritation  of  the  peripheral  appa- 
ratus may  be  assumed.  Gottlieb,  according  to  whom  the  increase  in  blood- 
pressure  depends  principally  upon  a  strengthening  of  the  cardiac  activity, 
after  investigations  in  chloralized  animals,  refers  this  to  an  energetic  irrita- 
tion of  the  motor  ganglion  groups  which  dominate  cardiac  movement.  Lewan- 
dowski  has  further  demonstrated  in  a  convincing  manner  a  peripheral  action 
of  the  injected  suprarenal  extract  upon  the  smooth  muscles  of  the  eye  and  of 
the  orbit  (dilatation  of  the  pupil,  prominence  of  the  hulbus  oculi,  etc.), 
which  is  parallel  to  the  vascular  action.  Finally  I  must  mention  the  local 
vaso- constricting  action  of  the  suprarenal  extract  which  has  been  lately  recog- 
nized, and  which  has  been  used  therapeutically  upon  the  conjunctiva  (by 
advice  of  Darier),  upon  the  larynx  and  nasal  mucous  membrane,  and  in 
intestinal  hemorrhages. 

In  several  of  the  investigations  it  has  been  proven  that  the  adrenal  venous 
blood  acts  similarly  to  the  extract  (Cybulski,  Dryer).  The  rise  in  blood- 
pressure  which  is  thus  attained  is  usually  very  decided.  In  some  cases  it 
has  been  raised  above  300  mm.  of  mercury.  After  destruction  of  the  spinal 
cord,  which  reduces  blood-pressure  almost  to  zero,  it  can  be  raised  to  160  mm. 
by  injection,  and  by  repeated  injection  the  pressure  can  be  maintained  for  a 
long  time  at  from  90  to  140  mm.  (Biedl).  By  using  a  very  pure  extract 
recently  produced  by  Moore  and  Purinton  jöooooo  °f  a  gram  is  sufficient 
to  maintain  in  a  dog  a  persistent  rise  in  blood-pressure  of  from  20  to  40  mm. 
of  mercury. 

Interesting  observations  have  recently  been  made  which  show  that  injection 
of  adrenal  extract  into  the  abdominal  cavity  of  guinea-pigs  causes  a  destruc- 
tion of  red  blood-corpuscles  and  produces  in  the  spleen  and  lymph-glands 


GROSSER  PATHOLOGICO-AXATOMICAL  LESIONS  209 

hemosiderin  deposits  similar  to  those  which  occur  in  the  so-called  hemo- 
chromatosis (a  pigmentation  of  the  skin  resembling  Addison's  disease)  (Foa). 
A  recent  experiment  is  also  to  be  mentioned  according  to  which  the  subcutane- 
ous (or  intravenous)  injection  of  adrenal  extract  in  animals  produces  glyco- 
suria in  the  majority  of  cases  (Blum). 

From  these  experiments  it  appears  that  we  must  admit  an  "  internal 
secretion"  of  the  suprarenals,  and  must  recognize  that  these  organs  furnish 
to  the  blood  a  substance  which  acts  primarily  To  raise  blood-pressure. 

Endeavors  to  isolate  and  more  minutely  to  characterize  the  substance  in 
the  adrenals  which  raises  blood-pressure  have  not  been  lacking.  These  have 
lately  led  to  definite  and  fixed,  even  though  not  always  uniform,  results. 
But  these  endeavors,  like  the  earlier  and  frequently  repeated  chemical  investi- 
gations of  the  adrenal  parenchyma,  are  not  calculated  to  advance  our  knowl- 
edge regarding  the  function  of  these  organs.  The  most  important  experi- 
ments are  the  following: 

The  earlier  investigations  (conducted  by  Yulpian  and  Virchow,  and  dating 
from  the  time  when  the  clinical  picture  of  Addison's  disease  was  first  made 
known)  were  made  with  a  substance  which  is  found  in  the  medulla  of  the 
adrenals  and  which,  with  iron  chlorid,  gives  a  blackish  green  color.  These 
observers  first  called  attention  to  the  similarity  of  the  pigment  seen  in  the 
parenchyma  of  the  adrenals  (particularly  in  the  intermediary  zone)  to  thai 
of  the  rete  Malpighii  in  pathologic  discoloration  of  the  skin.  Furthermore, 
observers  bave  made  frequenl  attempts  tu  isolate  a  peculiar  coloring  matter 
from  the  parenchyma  of  the  adrenals  hut  without  reaching  unanimous  results. 
Some  writers  emphasize  the  brown  coloration  of  the  tissue  (particularly  in 
the  intermediary  /.one)  which  occurs  with  >alt<  of  chromic  acid.  Several 
others  have  noted  -mall  globular  -tinctures  in  the  blood  of  the  adrenal  veins. 
These  granules  can  he  colored  with  chromic  acid,  and  bave  been  looked  upon 
as  product-  of  secretion  of  the  organs.  A  chromogen  with  differenl  deriva- 
tives ha-  been  found  by  several  observers  in  the  parenchyma;  by  some  this 
ha-  been  believed  to  he  identical  with  bemochromogen   (McMunn). 

Among  the  substances  which  have  I □  demonstrated  in  the  parenchyma 

of  the  adrenals  are  leiicin  and  myelin  which  were  referred  to  in  earlier  re- 
ports, lecithin  which  has  been  found  in  large  amounts  (Alexander),  a  related 
body  resembling  jecorin  which  contains  sulphur  and  phosphorus  (Manasse), 
and  neurin.  All  these  are  -ub-taiice-  from  the  presence  of  which  certain 
relation-  between  the  adrenals  and  nervous  Bystem   may  he  inferred.     The 

substance-  which  give  a  green  color  with  iron  have  been  found  to  be  chemically 
closely  related  to  pyrocatechin  (Krukenberg),  and  from  the  extract-  of  the 
medullary  Bubstances  it  i-  possible  to  isolate  a  compound  from  which,  by 
boiling  with  hydrochloric  acid,  pyrocatechin  can  he  produced  (Mühlmann). 
These  findings  also  indicate  a  relation  with  pigmentation  of  the  -kin  without 
furnishing  definite  proof  of  it. 

The  "substance  forming  a  green  color  with  iron"  and  the  "substances 
resembling  pyrocatechin "  are  identical  with  the  products  which  cause  n  rise 
in  blood-pressure,  and  for  use  a-  substitutes  for  the  adrenal  extract  in  animal 

injections  have  l d  produced  from  the  organs  by  complicated  chemical  proc- 

15 


210  ADDISON'S  DISEASE 

esses.  Of  the  numerous  investigations  of  this  character  which  have  recently 
been  conducted  three  must  be  particularly  mentioned:  One  of  these  bodies 
has  become  known  as  "  sphygmogenin  "  (Fränkel)  and  is  a  syrupy  substance 
which  shows  marked  reducing  property,  is  easily  oxidized,  and  with  a  watery 
iron  chlorid  solution  gives  a  dark  green  reaction.  Another  substance  named 
"  epinephrin  "  has  been  obtained  by  Abel  from  a  watery  extract  of  the  adre- 
nals as  a  benzoyl  combination.  As  a  result  of  elementary  analysis  Abel  looks 
upon  it  as  an  alkaloid  belonging  to  the  pyrrhol  or  skatol  group,  and  obtains 
from  it  by  treatment  with  dilute  alkali  a  dark  pigment.  Finally,  v.  Fürth, 
after  prolonged  study,  believes  he  has  found  a  still  purer  body  which  he  calls 
"  Suprarenin,"  and  designates  as  a  dioxypyridin  having  a  composition  of 
C5H.N02  or  C5H9!Sr02.  This  substance  also  raises  blood-pressure  upon  sub- 
cutaneous injection.  How  far  the  previously  mentioned  bodies  actually  repre- 
sent the  important  secretions  furnished  by  the  adrenals  to  the  blood  must 
be  decided  by  further  physiologico-chemical  investigations. 

After  this  brief  description  of  the  results  which  have  been  obtained  from 
experiments  and  chemical  investigation  in  regard  to  the  physiologic  action  of 
the  adrenals,  we  return  to  the  question:  Can  the  clinical  picture  of  typical 
Addison's  disease  be  explained  from  the  lesion,  that  is,  from  the  destruction 
of  these  organs? 

Up  to  a  certain  point  an  affirmative  answer  may  at  once  be  given.  We 
can  reconcile  many  important  symptoms  of  the  disease  with  a  gradual  decrease 
and  final  cessation  of  function  which,  from  the  experience  we  have  gathered, 
may  be  ascribed  to  the  adrenals,  and  we  can  find  abundant  analogies  between 
the  condition  of  the  person  attacked  by  Addison's  disease  and  the  experimental 
animal  that  has  been  deprived  of  its  adrenals. 

First  of  all  we  recognize  in  the  steadily  progressive  constitutional  disease 
which  leads  to  death  the  same  consequences  of  the  loss  of  vital  organs  which 
we  found  in  the  experiments.  That  the  duration  and  course  here  correspond 
but  little  with  those  in  the  animal  experiments  is  not  surprising.  Earely 
does  experimental  disease  in  the  animal  accurately  simulate  the  human  dis- 
ease, and  still  less  so  when,  as  in  this  case,  the  sudden  removal  of  the  organs 
from  the  animal  (even  should  the  extirpation  in  part  be  undertaken  at  two 
different  times)  is  contrasted  with  a  chronic  disease  in  the  human  being  with 
very  gradual  loss  of  function.  The  duration  of  the  disease  in  the  human 
subject  is  often  many  years — indeed  disturbances  of  the  adrenals  are  some- 
times of  such  long  standing  that  in  the  last  periods  of  life  a  complete  loss  of 
function  of  the  organ  must  be  assumed.  Nevertheless  we  can  sometimes  find 
analogy  for  this  in  the  circumstance  that  for  many  months,  even  for  years, 
it  is  possible  to  keep  the  experimental  animal  alive.  The  nature  of  the  general 
disease  in  both  cases  is  similar:  In  both,  emaciation  is  present,  but  is  not  the 
predominant  symptom;  in  both  the  signs  of  true  anemia  are  usually  of  mod- 
erate degree.  Against  this  the  general  asthenia,  the  permanent  and  increas- 
ing weakness  of  most  muscle  groups,  becomes  particularly  prominent  in  the 
clinical  picture,  and  reminds  us  strongly  of  the  prostration  which  appears 
so  constantly  in  the  experimental  animal. 


GROSSER   PATHOLOGICO-AXATOMICAL  LESIONS  211 

This  asthenia  in  Addison's  disease  may  also  he  alleged  as  valuable  proof 
of  the  theory  of  many  observers  that  the  function  of  the  adrenals  mainly 
consists  in  the  maintenance  of  the  muscular  tonus. 

The  cardiac  weakness  so  frequently  noted  in  Addison'-  disease,  which 
numerous  authors  have  also  observed  in  the  animals  operated  upon,  may  in 
some  respects  be  regarded  as  a  part  of  the  general  muscular  weakness.  Obvi- 
ously this  must  be  looked  upon  as  an  expression  of  the  fad  thai  a  disturbance 
of  the  adrenals  has  decreased  or  abolished  the  formation  of  a  substance  which 
increases  blood-pressure  and  strengthens  the  heart,  and  which  according  to 
the  investigations  we  have  mentioned  must  be  ascribed  to  the  parenchyma 
of  the  organ. 

In  regard  to  the  manifold  disturbances  originating  in  the  digestive  canal 
and  its  surroundings,  practical  experience  at  the  bedside  coincides  with  experi- 
mental results  and  theoretic  deductions:  The  majority  of  the  gastric  symp- 
toms, such  as  general  dyspepsia,  particularly  loss  of  appetite,  gastric  oppres- 
sion, eructations,  nausea,  vomiting,  etc.,  may  be  referred  to  the  general 
affection  with  its  adynamia,  anemia,  etc.  The  epigastric,  hypochondriac,  and 
lumbar  pains  which  arc  never  absent,  and  occasionally  form  the  most  distress- 
ing of  the  subjective  symptoms,  may  he  directly  due  to  pathologic  processes 
in  the  adrenals  themselves.  Experimental  investigators  have  repeatedly  de- 
mon-) rated  that  the  adrenal,  particularly  its  medullary  substance,  is  very  sensi- 
tive to  pain.  The  frequency,  too,  with  which  the  adrenal  affection  attacks 
the  surrounding  areas,  in  which  are  found  signs  of  old  local  peritonitis  in  the 
form  of  adhesions  and  connective  tissue  masses,  certainly  point-  to  a  similar 
explanation  of  these  pains.  Bui  though  we  cannot  be  sure  of  the  connection 
between  these  pains  and  the  chronic  and  progressive  inflammation,  a  terminal 
Btage  of  the  Addison  symptom  complex  resembling  peritonitis  has  of  late  been 
frequently  described  |  Ebstein).  To  explain  the  intestinal  symptoms,  the  same 
factors  may  suffice,  bul  we  may  also  call  to  mind  the  above-mentioned  experi- 
ment- which  -how  a  nervous  connection  between  the  adrenals  and  the  intes- 
tinal ganglia  and  suggesl  that  tnhibitive  nerve  impulses  are  normally 
transmitted  from  the  adrenals  to  the  intestine,  bo  as  to  control  intestinal 
movements.  The  diarrhea  which  appeal'-  in  the  terminal  stage  of  the  disease 
is  a  particularly  strong  argumenl   for  this  view. 

It  is  less  easy  to  ascribe  to  a  simple  adrenal  defect  some  of  the  many 
nervous  phenomena  which  accompany  the  disease.  The  general  nervous  symp- 
toms and   the  milder  form-  of  cerebral   implication  such  as  apathy,  headache. 

insomnia,  vertigo,  attack-  of  syncope  and  the  like  may  be  related  to  the  ady- 
namic and  anemic  general  condition.  Nevertheless,  these  symptoms  are  often 
much  greater  than  can  be  accounted  for  by  the  general  asthenic  condition-; 
for  example,  the  apathy  often  changes  into  increasing  psychical  depression 
with  disturbance  of  the  mental  function-,  showing  itself  partly  by  somnolence, 
partly  by  irritability.  To  this  may  be  added  the  neuralgic  condition-  often 
observed  in  the  earliesl  Btages,  especially  affecting  the  extremities  and  the 
joints,  and  finally,  the  usually  spasmodic,  often  epileptiform  attack-,  accom- 
panied  by  extreme  irritability  and  delirium   which   lead   up  to  the  final   coma 

of  the  later  course.     If  this  picture  i-  considered,  it  corresponds  neither  to  a 


212  ADDISON'S   DISEASE 

general  nutritive  disturbance  nor  to  a  simple  chronic  intoxication;  on  the 
contrary,  in  many  particulars  it  points  to  a  direct  implication  of  various  areas 
of  the  nervous  system. 

Most  difficult  of  all  to  understand  is  the  principal  clinical  symptom,  the 
bronzing  of  the  skin.  It  must  first  be  pointed  out  that  in  many  investigations 
of  extirpation  of  the  adrenals  in  animals,  even  in  those  animals  which  were 
kept  alive  a  long  time,  this  symptom  could  never  be  produced.  But  too  much 
stress  is  not  to  be  laid  upon  this  point,  for  there  is  justification  for  the  view, 
shared  by  many  observers,  that  the  comparatively  early  death  of  the  animals 
experimented  upon  may  have  checked  the  deposition  of  pigment.  Further, 
we  do  not  know  whether  abnormal  pigmentation  of  the  skin  occurs  in  animals 
as  readily  as  in  man. 

But  neither  do  our  investigations  furnish  anything  which  can  be  looked 
upon  as  proof  that  by  destruction  of  the  adrenals  pigmentation  of  the  skin 
is  directly  caused  or  even  favored.  We  may  concede  most  readily  the  possible 
truth  of  the  theory  (which  is  frequently  expressed)  that  under  normal  condi- 
tions there  is  a  substance  circulating  in  the  body  which  furnishes  material 
favoring  pigmentation,  but  which  is  rendered  inoperative  by  the  internal 
secretion  of  the  adrenals.  That  the  chemical  investigation  of  the  parenchyma 
of  the  adrenals  has  furnished  no  positive  points  of  support  for  this  has  already 
been  mentioned.  Such  a  connection,  too,  is  untenable  without  a  demonstrable 
pathologic  change  in  certain  fluids  of  the  tissues  and  in  the  blood;  for  such 
demonstration,  however,  there  is  no  further  experimental  evidence,  for  exam- 
ple, in  the  blood  and  in  the  urine. 

Of  the  blood  it  has  already  been  stated  that  an  estimation  of  the  blood- 
corpuscles  and  the  amount  of  hemoglobin  shows  for  the  most  part  but  slight 
change,  and  upon  exact  counting  of  the  leukocyte  varieties  no  important 
deviation  from  the  normal  has  been  found.  In  these  investigations  signs  of 
abnormal  amount  of  pigment  of  the  white  blood-corpuscles  or  of  the  serum, 
analogous  to  melanemia,  have  never  been  observed,  nor  does  the  finding  of 
cells  containing  blood-corpuscles  and  pigment  granules  in  the  marrow  of  the 
tubular  bones,  mentioned  in  one  case,  permit  positive  conclusions.  Nor  is 
much  added  to  our  knowledge  by  certain  reports,  according  to  which  there  is 
a  qualitative  change  in  the  blood  with  increase  of  reduced  hemoglobin  and 
appearance  of  methemoglobin  (Tschirkoff). 

Even  slighter  deviations  from  the  normal  were  shown  by  the  urine  in 
most  cases.  Apart  from  polyuria,  which  is  not  infrequently  noted,  in  some 
patients  an  increase  in  indican,  and  in  one  a  decided  increase  of  urobilin,  has 
been  found.  In  one  case  an  abnormal  coloring  material  ( urohematoporphy- 
rin)  was  determined  spectroscopically  (McMunn).  Furthermore,  there  are 
reports  regarding  decrease  of  urea  and  Creatinin.  Opposed  to  this,  however, 
are  a  large  number  of  reports  of  cases  in  which  a  normal  condition  of  the 
principal  urinary  constituents,  particularly  of  indican,  of  urea  or  nitrogen, 
has  been  determined.  A  new  amin  base  (Ewald)  obtained  from  the  urine 
in  a  single  instance  has  not  been  satisfactorily  explained. 

Nevertheless  while  there  is  no  evidence  which  points  with  certainty  to  a 
direct  importation  of  the  pigment  from  the  adrenals  to  the  skin,  the  possibility 


GROSSER  PATHOLOGICO-AXATOMICAL   LESIOXS  213 

of  a  process  of  this  kind  cannot  as  yei  be  excluded.  For  the  formation  of 
pigment  in  the  organism  is  a  complicated  process,  and  no  less  so  its  deposi- 
tion in  the  tissues,  particularly  in  the  skin.  Regarding  the  latter  process 
we  are  quite  well  informell  by  recent  investigations,  which  shall  briefly  be 
referred  to  here. 

According  to  these,  the  pathologic  deposition  of  pigment  in  Addison's 
disease  occurs  in  the  same  manner  as  physiologic  discoloration  of  the  skin 
(in  dark  races,  in  pregnancy,  etc.)  winch  is  apparently  distributed  in  an 
analogous  manner  also  in  all  species  of  animal-.  The  main  seat  of  the  pig- 
ment  particles,  all  observers  who  have  undertaken  microscopic  investigations 
of  the  bronzed  skin  find  to  be  the  cells  of  the  lowest  layers  of  the  rete  Mal- 
pighii.  The  previous  view  that  the  pigment  development  here  is  autochtho- 
nous (by  metabolic  activity  of  the  cells)  has  been  almost  wholly  abandoned. 
On  the  contrary,  quite  a  number  of  recent  investigators  (Renaut,  Nothnagel, 
Riehl,  v.  Kahlden  and  others)  have  proved  conclusively  that  the  pigment  from 
the  deeper  layers  of  the  corium  is  brought  to  the  rete  cells  by  motile  cells. 
and  that  the  pigment  most  probably  originates  in  the  blood.  The  findings 
resemble  one  another  very  much  in  individual  cases;  almost  always,  beneath 
the  pigment  layer  of  the  rete.  wandering  cells  are  to  be  seen  carrying  pigment 
through  the  corium;  in  the  deeper  cutis  Layers  these  cells  often  accumulate 
in  large  groups  around  the  vessels,  partly  also  in  their  adventitia.  A  disease 
of  the  walls  of  the  vessels  has  been  described  in  several  cases,  in  which  swelling, 
cellular  infiltration  and  small  hemorrhages  were  conspicuous  (Riehl),  but 
this  has  not  heen  discerned  by  other  observers,  and  does  not  appear  to  play 
a  role  in  the  process.  The  mucous  membrane  of  the  mouth  shows  conditions 
analogous  to  those  of  the  cutis. 

It  is  obvious  that  this  process  of  pigment-deposil  in  the  skin  favors  the 
assumption  of  an  abnormal  coloring  material  admixed  with  the  blood  as  the 
result  of  adrenal  disease,  a  chromogen,  for  the  existence  of  which,  however 
(as  I  have  previously  Baid  with  emphasis),  our  knowledge  up  to  this  time 
gives  no  points  of  support,  it  must  also  be  remembered  that  if  there  were  such 
an  over-flooding  of  the  vascular  system  with  pigment  it  would  be  very  difficult 
to  explain  why  no  deposits  of  pigment  are  found  in  any  areas  of  the  internal 
organs.  At  any  rate,  it  is  obvious  that  besides  the  hypothesis  of  the  trans- 
portation of  pigment  from  the  Mood  to  the  superficial  layers  of  the  skin  we 
should  also  consider  the  possibility  that  the  disease  may  be  due  to  an  implica- 
tion of  the  nervous  system,  upon  whose  vasomotor  and  trophic  tracts  the  walls 
of  the  vessels  and  the  cells  of  the  cutis  are  dependent  to  a  high  degree. 
Evidently  the  unusual  formation  of  pigment  substance  from  the  hemoglobin 
(normal  or  modified),  and  the  increased  activity  of  the  cells  transporting 
the  pigment,  can  scarcely  occur  without  the  uerve  elements  being  subjected 
to  an  abnormal  irritation.  Also  many  irregularities  of  the  pigmentation  of 
the  skin  occurring  in  Addison's  disease,  particularly  the  not  infrequent  occur- 
rence of  leukoderma  plaques,  as  well  as  the  combination  with  other  trophic 
cutaneous  disturbances  (sclerodema),  point  to  varying  local  processes  of  in- 
nervation. Finally,  it  is  not  without  significance  to  remember  that  in  many 
specie-  of  animals  characterized  b)  conspicuous  staining  of  the  -kin  (chame- 


214  ADDISON'S  DISEASE 

leons,  frogs,  etc. )  the  dependence  of  "  ehroinoblasts  "  upon  the  nervous  system 
(Kaymond)  has  been  proven. 

Thus  the  most  conspicuous  symptom  of  Addison's  disease  points  with  more 
emphasis  than  any  of  the  others  to  an  implication  of  the  nervous  system. 
Therefore  we  are  forced  to  the  conclusion  that  even  in  the  most  typical  cases 
a  conception  of  the  clinical  picture  as  due  to  a  cessation  of  suprarenal  func- 
tion is  beset  with  difficulties. 

The  perplexities  of  explanation  increase  materially  when  we  leave  the  realm 
of  purely  typical  cases  of  Addison's  disease,  and  consider  the  deviations  which 
the  clinical  symptoms  and  pathologico-anatomical  findings  present  under  some 
circumstances.  Unfortunately,  these  variations  from  the  normal  type  of  the 
disease  are  not  very  rare.  I  mean  by  this,  not  the  many  quantitative  differ- 
ences in  individual  symptoms  whereby  it  often  occurs  that  one  symptom,  for 
example,  gastro-intestinal  phenomena,  becomes  more  marked  than  all  others, 
or  that  the  bronzing  of  the  skin  is  very  intense  in  the  early  stages  of  the 
disease,  while  at  other  times,  toward  the  termination  of  the  affection,  it  is 
only  very  moderate,  that  at  the  autopsy  the  adrenals,  contrary  to  rule,  are 
found  with  lesions  of  fresh  degeneration,  and  in  part  present  well  retained 
parenchyma  and  the  like.  All  these  variations  depend  upon  the  duration, 
course  and  complications  of  the  disease,  and  partly  upon  auxiliary  conditions 
which  cannot  be  controlled.  Much  more  important  are  the  instances  of  a 
lack  of  coincidence  between  the  main  clinical  symptom,  the  pigmentation  of 
the  skin,  and  the  important  factor  of  the  pathologico-anatomical  picture — 
the  degeneration  of  the  adrenals.  Such  exceptions  were  noted  soon  after  the 
publication  of  Addison's  fundamental  description,  and  have  multiplied  in 
the  course  of  years,  so  that  many  modern  authors  deny  wholly  the  parallelism 
between  the  pigmentation  of  the  skin  and  adrenal  disease. 

Two  groups  of  cases  are  here  to  be  distinguished,  and  by  most  observers 
have  been  noted  separately:  The  cases  in  which  in  well  developed  Addison's 
disease  with  bronzing  no  affection  of  the  adrenals  has  been  shown,  and  upon 
the  other  hand,  advanced  changes  in  the  adrenals  without  discoloration  of  the 
shin  and  even  in  some  cases  without  any  severe  symptoms.  The  frequency 
of  such  exceptions  naturally  cannot  be  seen  in  a  small  group  of  cases,  and 
full  compilations  have  up  to  the  present  time  been  very  rarely  made  (Aver- 
beck, Greenhow,  G.  Lewin).  Among  the  earlier  reports  of  this  kind  Green- 
how's  statistics  are  to  be  referred  to,  in  which  among  172  cases  of  undoubted 
Addison's  disease,  disease  of  the  adrenals  was  absent  in  10.  The  most  com- 
plete compilation  at  present  is  that  of  Lewin,  which  includes  561  autopsies; 
according  to  this,  typical  Addison's  disease  with  changes  in  the  adrenals  is 
noted  in  88  per  cent.,  without  lesion  in  12  per  cent.;  on  the  other  hand  there 
was  adrenal  disease  with  bronzing  of  the  skin  in  72  per  cent.,  without  such  in 
28  per  cent,  of  the  cases.  Now  it  must  be  stated,  once  for  all,  that  most 
statistics  of  this  kind  which  refer  to  early  cases  are  unreliable  on  account 
of  the  lack  of  defmiteness  in  the  descriptions  of  the  pathologico-anatomical 
conditions  of  the  adrenals.  In  some  cases  disease  of  the  adrenals  has  doubt- 
less been  overlooked,  in  others  erroneously  assumed.    Nevertheless  the  number 


PATHOLOGICO-ANATOMICAL  CHANGES   OF  THE   NERVOUS  SYSTEM    215 

of  these  deviations  from  the  supposed  pathology  of  Addison's  disease  is  too 
great  for  us  to  ignore. 

For  us  the  exceptional  cases  in  which  the  clinical  picture  of  Addison's 
disease  does  not  correspond  with  the  adrenal  affection  are  of  the  greatest 
importance.  They  are  the  ones  which  even  in  early  years  caused  doubts  to 
arise  regarding  the  direct  dependence  of  the  clinical  picture  upon  disease  of 
the  adrenals,  and  soon  caused  investigators  to  search  for  another  explanation 
of  many  of  the  pathologico-anatomical  findings.  That  the  first  point  of 
attack  was  usually  an  investigation  into  the  nervous  system  is  not  surprising 
when  we  consider  the  location  and  intimate  connection  of  certain  parts  of  the 
nervous  system,  particularly  the  abdominal  sympathetic  plexus,  with  the  adre- 
nals. At  autopsies,  special  attention  has  apparently  been  directed  to  these 
parts  by  the  frequent  extension  of  the  disease  of  the  adrenals  to  the  surround- 
ing areas,  often  in  the  form  of  circumscribed  inflammation  and  connective 
tissue  development,  more  rarely  in  the  form  of  tumor  formation;  particularly 
in  important  nerve  areas.  Thus  in  the  last  decades  a  greal  number  of  ana- 
tomical investigations,  partly  superficial,  partly  very  thorough,  have  been 
made  of  the  nervous  apparatus  surrounding  the  adrenals,  and  a  great  number 
of  results  have  been  obtained,  the  most  important  of  which  will  now  be 
briefly  sketched. 

PATHOLOGICO-ANATOMICAL   CHANGES  OF  THE  NERVOUS  SYSTEM 

IN   ADDISON'S   DISEASE 

The  parts  of  the  nervous  Bystem  most  frequently  investigated,  and  most 
frequently  found  diseased,  are  the  semilunar  ganglia  of  the  solar  plexus. 
These  are  naturally  Implicated  by  a  circumscribed  peritonitis  or  insidious 
connective  tissue  inflammation  developing  from  the  adrenals;  and  thus  we 
find  a  decided  percentage  of  cases  in  which  these  ganglia  are  reported  as 
adherent  to  their  surroundings,  enclosed  by  connective  tissue  proliferation,  or 
embedded  in  cicatricial  tissue.  It  may  also  be  assumed  that  these  conditions 
are  even  more  frequenl  than  the  records  show  since  in  the  protocols  of  the 
earlier  observers,  adhesions  and  peritoneal  remains  have  often  been  reported 
as  presenl  in  the  surroundings  of  the  adrenal-  without  the  sympathetic  plexus 
being  menl  ioned. 

In  other  cases  it  is  stated  thai  in  spite  of  the  connective  tissue  embedding, 
normal  nerve  elements  have  been  demonstrated  in  the  plexus;  yel  it  remains 
questionable  whether  these  findings  included  all  areas  of  the  nervous  organs, 
and  also  whether  nerve  elements  pressed  upon  by  tissue  of  this  kind  may  be 

looked    upon   as    functionally   normal.      Such   connective  tissue   proliferation    is 

closely  analogous  to  a  compression  of  the  sympathetic  plexus  by  tumors  (tuber- 
culous, carcinomatous,  or  Leukemic)  or  by  aneurism  of  the  aorta. 

With  or  without   such  disease  of  the  surrounding  tissue,  the  semilunar 
ganglia  have  shown  man\   macroscopic  and  microscopic  changes.    The  macro- 
pic  alterations   have   been    noted   either  as   enlargement,   thickening   and 
swelling  (and  at  this  not  always  of  the  ganglia  themselves  but    frequently 
also  of  the  nerve  bundles  extending  Erom  them  to  the  adrenal-)  with  hyper- 


216  ADDISON'S  DISEASE 

eniia  and  abnormal  succulence;  also  decrease  in  size,  atrophy  and  induration. 
In  some  cases  the  ganglia  have  been  implicated  in  a  process  of  caseation 
(tumor  formation  is  also  mentioned).  Histologic  investigations  have  shown 
the  signs  of  fresh  or  older  inflammation  and  degeneration  with  their  conse- 
quences, particularly  interstitial  connective  tissue  proliferation,  cellular  infil- 
tration and  thickening  of  the  capsules  of  the  ganglion  cells  and  nerve  sheaths ; 
moreover,  abnormal  pigmentation  of  many  tissue  elements,  fatty  degeneration 
and  pigment  atrophy  of  the  ganglion  cells  (occasionally  reaching  a  very  high 
grade).  Finally  there  are  observations  of  various  forms  of  neuritis,  atrophy 
and  degeneration  of  the  nerve  fibers  traversing  the  ganglia  and  proceeding 
from  them.  Conspicuous  vascular  changes  (thickening  and  hyaline  degenera- 
tion of  the  walls  of  the  vessels,  accumulation  of  cells  and  hemorrhages  in  the 
adventitia)  have  also  been  noted,  particularly  in  the  areas  near  the  adrenals 
(v.  Kahlden). 

The  same  changes  (thickening,  contraction,  degeneration  of  ganglion  cells 
and  nerve  fibers)  have  also  been  frequently  found  in  other  parts  of  the 
solar  plexus. 

Various  observers  note  far-reaching  degeneration  of  the  splanchnic  nerve, 
partly  in  the  form  of  fresh  or  older  neuritis,  partly  as  gray  degeneration  of 
the  medullary  fibers,  the  latter  sometimes  as  consequences  of  compression; 
for  example,  by  an  aneurism  of  the  aorta  (Jürgens). 

Similar  neuritic  disease  has  been  found  in  the  sympathetic  system,  some- 
what removed  from  the  adrenals,  particularly  in  the  boundary  column  of  the 
sympathetic  and  in  its  cervical  ganglia.  The  former  has  often  been  found 
conspicuously  thickened  and  indurated,  the  latter  decidedly  swollen,  and  show- 
ing inflammatory  changes.  Fleiner  was  able  to  follow  similar  processes  of 
the  disease  through  a  large  part  of  the  sympathetic  nervous  system,  and  also 
in  two  cases  in  the  central  nervous  system.  These  findings  are  the  more 
convincing  as  in  both  cases  they  were  quite  similar,  while  the  nature  of  the 
disease  differed  decidedly  (one  was  dependent  upon  tuberculosis  of  both  adre- 
nals, and  the  other  upon  Sarcomatosis  of  an  adrenal  and  its  surroundings). 
In  both  instances  a  chronic  process  of  inflammation  could  be  demonstrated 
which  extended  from  the  diseased  adrenals  through  the  semilunar  ganglion 
to  the  boundary  column  of  the  sympathetic  with  its  thoracic  and  cervical 
ganglia  into  the  pneumogastric,  and  was  particularly  well  developed  in  the 
intervertebral  ganglia  of  the  posterior  thoracic  and  upper  lumbar  portions  of 
the  vertebral  column.  In  all  of  these  areas  there  was  found  diffuse  connective 
tissue  proliferation,  or  focal  accumulation  of  round  cells  in  the  neighborhood 
of  vessels ;  besides  this  markedly  intense  pigment  atrophy  of  the  ganglion 
cells,  and  extensive  degeneration  of  medullary  fibers  in  the  sympathetic,  the 
splanchnics  and  also  in  the  vagus.  In  the  spinal  ganglia  the  nerve  fibers 
showed  advanced  degeneration,  most  markedly  in  the  nerve  branches  leading 
to  the  sympathetic,  less  so  in  those  leading  to  the  posterior  roots  of  the  spinal 
cord.  Finally,  the  same  degenerative  processes  were  found  in  a  number  of 
peripheral  nerves,  chiefly  in  the  sensory  cutaneous  branches. 

In  the  spinal  cord  the  same  observer  found  no  important  changes,  but  such 
have  repeatedly  been  described  by  others  (Burresi,  Babes  and  Kalindero,  etc.). 


PATHOLOGICO-ANATOMICAL  CHANGES  OF  THE  NERVOUS  SYSTEM    217 

and  especially  in  the  dorsal  cord.  The  changes  consist  partly  of  hyperemia 
and  round  cell  accumulation,  partly  of  sclerosis  with  thickening  of  the  neu- 
roglia and  of  the  walls  of  the  vessels,  also  atrophy  of  the  ganglion  cells  and 
neuritic  processes  in  the  spinal  roots  (particularly  the  posterior  ones). 

It  must  also  be  mentioned  that  by  some  authors  special  stress  is  laid  upon 
disease  of  the  small  pericapsular  adrenal  ganglia  which  are  frequently  impli- 
cated by  the  local  process. 

Many  of  these  reports  have  been  met  by  the  criticism  that  the  importance 
of  the  patholbgico-anatomical  changes  has  been  exaggerated,  and  that  many 
of  them  do  not  go  beyond  what  we  have  learned  to  recognize  by  more  recent 
investigations  as  the  consequence  of  general  nutritive  disturbances  produced 
by  many  forms  of  anemia,  cachexia  and  the  like  in  the  elements  of  the  nervous 
system.  This  criticism  can  only  refer  to  the  mild  degrees  of  such  changes, 
as  the  atrophy  of  the  ganglion  cells  and  nerve  fibers,  the  pigmentation  of 
tissue  elements,  etc.;  and  I  do  not  intimate  that  the  importance  of  changes 
such  as  these  is  to  be  denied.  It  is.  however,  different  with  the  severer  findings 
reviewed  above,  in  which,  as  a  rule,  advanced  degenerative  conditions  of  the 
cellular  element-  are  combined  with  conspicuous  inflammatory  processes  of 
the  inter-! it ial  tissue.  Such  changes  must  be  counted  among  the  characteristic 
findings  of  the  disease  in  question,  and  must  be  considered  in  judging  of  its 
pathogene-i-. 

It  is  true  that  our  limited  knowledge  makes  it  difficult  to  estimate  the 
relative  frequency  of  such  pathologic  nerve  findings.  Judging  from  the  mate- 
rial at  hand,  we  cannot  look  upon  them  a-  constant.  For  quite  a  number  of 
reports  are  diametrically  opposed  to  those  just  mentioned,  ami  show  that, 
in  the  investigation  of  certain  areas  of  the  nervous  system,  no  abnormality 
had  been  found.  It  i-  true  a  Large  number  of  these  communications  arc  Ear 
removed  from  being  susceptible  of  general  proof.  First,  there  are  some  of 
them,  particularly  dating  from  earlier  periods,  in  which  the  anatomical  inves- 
tigation regarding  the  more  minute  relation  of  the  nerve  elements  was  insuffi- 
cient. It  need  only  be  mentioned  here  that  in  many  of  the  earlier  cases  it 
was  decided  macroscopically  whether,  for  example,  the  semilunar  ganglia 
were  of  normal  Bize,  color,  consistence  and  the  like.  Then  the  majority  of 
these  investigations  refer  only  to  -mall  areas  of  the  nervous  Bystem;  few 
among  them  follow  completely  the  important  central  part-  of  the  sympathetic 
-v-tein.  and  investigate  whether  the  neighboring  areas  of  the  central  nervous 
-v-tein  are  al-o  implicated.     In  the  overwhelming  majority  of  cases  only  the 

lunar  ganglion  and   -olar  plexus  have  I n  examined:   much   more  rarely 

the  splanchnics  and  the  boundary  column  between  the  dorsal  ganglion  and  the 

cervical  ganglion  of  the  sympathetic  have  1 n  examined.    The  intervertebral 

ganglia,  upon  which  lately  special  stress  ha-  been  laid,  as  well  as  upon  the 
spinal  roots  and  the  spinal  cord,  have  Keen  l,ut  very  rarely  investigated  except 
in   the   few  cases  mentioned   above.     It   may  he  added   that   these  negative 

report-    la-   well   a-   the   po-itive   nerve   findings)    occurred   usually    in   eases   in 

which  the  adrenals  Bhowed  no  conspicuous  change. 

Here,  therefore,  are  flaws  and  doubts  which  can  he  removed  only  by  con- 
tinued and  thorough  histologic  investigations  of  a  large  number  of  additional 


218  ADDISON'S  DISEASE 

cases.  Nevertheless,  in  judging  these  cases  impartially,  the  impression  is 
received  from  the  reports  which  have  been  published  regarding  the  condition 
of  the  nervous  system,  especially  of  the  sympathetic,  in  Addison's  disease, 
that  there  is  decidedly  more  in  favor  than  against  the  presence  of  important 
disease  of  these  tissues.  This  opinion  coincides  with  the  results  of  a  later 
English  compilation  (Thompson)  ;  here  among  77  records  which  included 
minute  histologic  investigations  of  sympathetic  nerve  areas,  important  changes 
were  noted  in  60. 

The  question  must  now  be  propounded  whether,  by  the  aid  of  these  anom- 
alies of  the  nervous  system,  determined  in  a  large  series  of  cases,  we  can  better 
explain  the  atypical  cases,  in  which,  with  true  Addison's  disease  (clinically), 
no  demonstrable  adrenal  affection  is  found  to  correspond.  This  question  must 
without  doubt  be  answered  in  the  affirmative.  As  regards  the  bronzing  of 
the  skin  it  has  already  been  indicated  that  for  its  development  we  must  assume 
an  implication  of  the  nervous  system,  especially  vasomotor  and  trophic  func- 
tions, even  in  the  cases  with  typical  pathologico-anatomical  findings.  A 
disease  of  the  essential  parts  of  the  abdominal  sympathetic  and  neighboring 
nerve  areas,  and  particularly  changes  in  these  processes  with  increased  forma- 
tion and  transportation  of  pigment  into  the  region  of  the  cutis  layers,  may 
be  very  readily  conceived.  In  this  connection  we  may  point  especially  to  the 
spinal  ganglion,  whose  influence  in  producing  trophic  changes  of  the  skin, 
according  to  clinical  and  experimental  investigations,  has  at  various  times 
been  especially  noted. 

If  then  no  additional  knowledge  concerning  the  connection  of  the  adrenals 
with  pigment  formation  in  the  body  is  obtained  by  further  investigations,  the 
pigmentation  of  the  skin  in  typical  Addison's  disease  (as  well  as  in  cases  with- 
out demonstrable  adrenal  affection)  will  therefore  probably  be  found  related 
to  changes  in  the  nerve  areas  in  question.  What  then  is  the  relation  of  the 
other  symptoms  of  the  disease  to  the  lesions  of  the  nervous  system  ?  May  they 
also  under  these  circumstances  be  referred  to  nervous  disturbance?  Up  to  a 
certain  point  such  an  explanation  does  not  appear  unlikely:  the  characteris- 
tic lumbar  and  epigastric  pains  of  Addison's  disease  are  almost  the  same  as 
those  which  have  long  been  referred  to  irritation  of  the  abdominal  sympathetic 
ganglion.  Furthermore  the  intestinal  symptoms  may  be  explained  by  irrita- 
tion or  paralyses  of  the  abdominal  nervous  system,  particularly  of  the  splanch- 
nic nerve,  and  the  cachexia  and  other  general  symptoms  may  be  in  part 
referred  to  nutritive  disturbance  due  to  changed  gastric  and  intestinal  func- 
tions. Naturally  the  picture  of  this  general  disturbance  (even  without  con- 
sidering the  pigmentation)  remains  a  peculiar  one,  such  as  we  are  not  accus- 
tomed to  see  in  most  cachexias.  And  if  we  look  upon  the  symptoms  of  the 
disease  as  a  result  of  disturbed  suprarenal  function  (particularly  the  charac- 
teristic muscular  weakness),  there  would  be  no  barrier  for  the  assumption  in 
these  cases  of  a  functional  disturbance  of  the  adrenals  as  a  consequence  of 
disease  of  the  nervous  areas  which  influence  glandular  activity. 

That  such  a  disease  of  the  nervous  system,  without  (or  only  with  a  sec- 
ondary)  implication  of  the  adrenals,  is  capable  under  certain  circumstances 


PATHOLOGICO-ANATOMICAL  CHANGES  OF  THE  NERVOUS  SYSTEM    219 

of  producing  the  picture  of  the  disease,  is  evident  from  the  rare  cases  which 
have  been  cited  in  which  compression  of  the  solar  plexus,  of  the  splanchnic 
nerves,  etc.,  by  tumors  (aneurisms  and  the  like)  has  been  the  basis  of  Addi- 
son's disease.  But  how  often  a  similar  affection  of  the  nervous  system  is  also 
present  (perhaps  late,  perhaps  from  the  outset)  in  the  cases  running  their 
course  with  adrenal  affection,  cannot  be  decided  at  this  time  on  account  of  our 
insufficient  knowledge  regarding  the  nervous  findings.  The  usual  course  of 
the  common  affection  will  probably  be  this,  that  the  affection,  mostly  inflam- 
matory, starting  from  Ihr  adrenal  attacks  Ihr  surroundings;  that  is,  first,  the 
semilunar  ganglion,  later,  the  other  parts  of  the  sympathetic,  eventually,  the 
cerebrospinal  nervous  system.  The  frequency  of  this  course  of  the  disease 
is  suggested  also  by  the  fact  that  those  adrenal  lesions  in  which  there  is  an 
insidious  inflammation  or  some  similar  process  which  attacks  the  adjacent 
areas  are  especially  apt  to  cause  Addison's  disease.  To  this  category  belong 
especially  the  tuberculous  affections  of  the  adrenals,  most  of  which  probably 
depend  upon  atrophies  due  to  older  inflammatory  processes;  also  certain 
tumors  which  cause  metastases.  With  the  majority  of  single  tumors  of  the 
adrenal  glands,  therefore,  there  is  no  Addison's  disease,  and  in  the  rare  cases 
of  adrenal  tuberculosis  without  Addison's  symptoms,  disease  in  the  surround- 
ings of  the  organs  has,  as  a  rule,  been  absent. 

Whether,  however,  the  form  of  disease  with  the  characteristics  of  Addi- 
son's disease,  which,  starting  from  the  adrenal  attacks  the  surrounding  area-. 
does  not  also  perhaps  cause  certain  changes  within  the  affected  nerve  areas 
bo  that  they  may  develop  independently,  we  cannot  say  on  account  of  our  lack 
of  pathologico-anatomical  knowledge.  It  must  be  assumed  that  under  some 
circumstances  an  analogous  but  independent  disease  of  llu>  nervous  system  may 
take  the  place  of  adrenal  disease  ami  produce  the  same  clinical  picture  entirely 
without  implication  of  the  adrenal-  or  with  only  a  late  involvemenl  of  the 
glands. 

Physiologic  experiments  have  failed  to  determine  the  matter  in  question. 
It  is  true  that  repeated  experiments  by  extirpation  (also  cauterization)  of  the 
semilunar  ganglia  have  been  attempted  without,  however,  furnishing  definite 
conclusions :  Previous  experiments  of  this  kind  (  Foä  )  have  been  entirely  with- 
out result;  and  in  a  more  recenl  series  of  investigations  (Lewin  and  Boer) 
in  animals  which  lived  thirty  days  or  Longer  after  the  operation,  only  paresis 
of  the  intestines,  usually  with  diarrhea,  hut  with  no  pigmentation  or  other 
characterisl ic  changes,  \\a-  aoted. 

The  researches  next  to  he  mentioned  relate  chiefly  to  cases  of  Addison's 
disease  (with  autopsy)  in  which  the  adrenal-  were  1 1 * > t  implicated,  but,  or 
the  other  hand,  certain  nerve  areas  were  attacked.  A  U~w  other  cases  remain 
in  which  the  autopsy  shows  no  important  changes  In  Ihr  mir, 'mils  ,nnl  none 
in  Ihr  nervous  system.  The  uumber  of  auch  cases  is  -mall,  ami  from  this 
group  many  mu-t  he  excluded  in  which  the  diagnosis  i-  questionable.  Of 
those  remaining  it  i-  uol  quite  certain  from  the  report-  that  all  of  the  uerve 
areas  were  considered  in  the  investigation  ami  that  it  was  sufficienl  to  exclude 
any  disease.  Whether,  and  how  often,  cases  of  this  kind  exist,  minute  histo- 
logic examination  of  -imilar  doubtful  <a-e-  mu-t   in  the  future  decide.      If  we 


220  ADDISON'S   DISEASE 

admit  their  occurrence,  they  cause  great  difficulty  in  explanation;  for  to 
assume  a  functional  disturbance  of  the  affected  nerve  areas,  and  perhaps  also 
of  the  adrenals,  without  any  anatomical  substratum,  would  be  very  unsatis- 
factory. It  may  be  assumed,  however,  that  cases  of  this  kind  will  always 
remain  rare  exceptions. 

The  group  of  cases  in  which  adrenal  disease  is  present  without  Addison's 
Symptoms,  particularly  without  bronzing  of  the  skin,  does  not  belong,  as  has 
already  been  stated,  to  the  disease  we  are  considering.  Nor  does  it  offer  im- 
portant reasons  to  vitiate  the  views  which  have  been  expressed  above.  In  the 
first  place,  we  usually  find  in  such  cases  affections  of  the  adrenals  which  are 
in  marked  contrast  to  typical  cases  of  Addison's  disease:  The  majority  of 
them  are  tumors  of  the  adrenal  glands  and  the  absence  of  Addison's  symptoms 
is  here  the  rule;  thus  a  recent  compilation  of  26  cases  of  primary  malignant 
tumors  of  the  adrenals  showed  that  the  clinical  picture  of  Addison's  disease 
was  invariably  absent.  In  most  of  the  other  cases  of  this  group  it  remains 
uncertain  whether  by  tumor  formation  or  other  disease  of  the  parenchyma  of 
the  adrenals  the  destruction  is  as  marked  as  is  the  rule  in  most  cases  of  tuber- 
culosis; the  areas  surrounding  the  glands  also  appear  to  remain  comparatively 
free.  Finally,  in  explanation  of  these  cases,  an  abnormally  great  development 
of  the  accessory  adrenals  may  be  thought  of. 

I  believe  the  considerations  above  adduced  will  suffice  to  make  it  obvious 
that,  according  to  the  pathological  and  clinical  material  at  our  disposal,  the 
clinical  picture  of  Addison's  disease  does  not  depend  exclusively  upon  a  grad- 
ual destruction  of  the  adrenals,  nor  exclusively  upon  a  disease  of  the  nervous 
system  (i.  e.,  the  abdominal  sympathetic  and  other  nerve  areas  intimately 
associated  with  it),  but  that  both  these  factors  are  simultaneously  active  in 
the  development  of  the  symptom-complex — a  view  in  which  I  coincide  with  a 
number  of  earlier  as  well  as  more  recent  investigators  (Fleiner,  Neusser  and 
others).  How  these  forms  of  the  disease  merge  into  each  other  is  very  difficult 
to  determine,  and  varies  evidently  to  an  extreme  degree.  A  particularly  fre- 
quent connection,  according  to  the  views  mentioned  above,  appears  to  be  a 
kind  of  ascending  disease,  which  spreads  from  the  adrenals  to  the  neighboring, 
and,  eventually  also,  to  the  more  distant  nerve  tracts;  that,  however,  opposite 
(descending)  processes  are  also  at  work  is  at  least  likely,  and  has  been  men- 
tioned previously.  Moreover,  there  need  be  no  parallelism  between  these 
pathologic  processes ;  on  the  contrary,  in  well  advanced  changes  of  the  adrenals 
very  slight  implication  of  the  nerves  may  be  found,  and  vice  versa ;  in  quite 
a  number  of  cases  according  to  present  experience,  the  disease  of  one  or  both 
parts  may  be  entirely  absent.  By  this  variation  in  the  relations  of  the  diseased 
areas,  we  may  very  readily  explain  the  great  variation  in  the  intensity  of  indi- 
vidual symptoms  and  in  the  time  of  their  appearance,  so  that,  for  example, 
the  bronzing  of  the  skin  may  occur  years  before  the  general  symptoms,  or, 
inversely,  the  general  disturbance  may  exist  for  a  long  time  without  pigmen- 
tation. 

If  a  definition  of  the  pathologico-anatomical  basis  of  Addison's  disease  is 
desired  it  may  be  given  in. the  following  form:  The  disease  depends  upon  an 
insidious,  partly  inflammatory,  partly  degenerative  affection  (most  frequently 


PATHOLOGICO-AXATOMICAL  CHANGES  OF  THE  NERVOUS  SYSTEM    221 

dependent  upon  tuberculosis),  which  implicates  first  the  parenchyma  of  the 
adrenals  and,  secondaritu.  certain  nerve  areas  ivhich  are  in  intimate  relation 
to  the  adrenals  (particularly  the  abdominal  sympathetic  and  some  nerve  areas 
connected  with  it.  perhaps  also  certain  portions  of  the  spinal  cord).  Since 
disease  of  both  of  these  regions  may  be  combined  in  various  ways,  and  may 
also  compensate  for  one  another,  the  peculiar  general  affection  develops  which 
represents  what  is  characteristic  of  Addison's  disease. 

I  believe  it  is  impossible  to  explain  in  a  more  definite  manner  tJie  nature 
of  this  general  disturbance  on  account  of  the  missing  links  in  our  present 
knowledge.  From  experimental  investigations,  and  also  from  the  clinical 
observations  which  have  been  outlined,  it  i-  evident  that  from  disease  of  the 
adrenals  a  deleterious  clement  appears  in  the  organism,  and  many  theories 
have  been  offered  to  explain  the  nature  of  Addison's  disease.  Almost  every 
one  of  these  is  plausible  up  to  a  certain  degree,  but  not  proven;  and  almost 
all  explain  only  a  few  of  the  important  phases  of  the  clinical  picture.  Which 
of  these  is  to  be  accepted  as  the  most  reasonable  is  merely  a  matter  of 
opinion  in  the  present  status  of  our  knowledge.  I  need  indicate  only  a  few 
of  these:  They  may  be  divided  in  general  into  the  "toxic"  and  "nervous" 
theories,  according  to  whether  the  changes  in  the  adrenals  or  those  in  the  nerv- 
ous system  have  been  assumed  to  be  the  more  important.  Of  the  first  group, 
recent  experiment-  have  made  it  seem  probable  that  after  extirpation  of  the 
adrenals  the  development  of  substances  resembling  muscle  poisons  take-  place 
in  the  organism.  They  assume  accordingly  that  the  normal  "  antitoxic  action," 
which  i-  said  to  be  a  function  of  the  adrenals,  declines  or  i-  entirely  absent  : 
hence  the  poisons  circulating  in  the  muscles  and  tissues  are  able  to  exert  their 
harmful  influence.  According  to  the  views  of  others,  the  diseased  adrenal 
it-elf  i-  supposed  to  furnish  the  toxin-  which,  by  their  circulation  in  the  fluids 
of  the  body,  produce  the  general  affection.  Other  theories  which  consider  a 
regulation  of  cell  nutrition  to  be  the  normal  function  of  the  adrenals  ascribe 
the  disease  to  the  development  of  toxic  products  by  an  abnormal  activity  of 
the  tissue  cells  which  thus  lead-  to  the  picture  of  a  general  intoxication.  The 
theory  i<  plausible  that,  in  consequence  of  the  absence  of  the  normal  function 
of  the  adrenals,  a  substance  i-  missing  in  the  fluids  which  should  give  to  the 
muscular  fibers  and  other  tissue  elements  the  tonus  necessary  for  their  normal 
functions.  Opposed  to  this  are  the  theories  that  the  disease  i-  one  of  the 
nervous  -y-teiii.  especially  of  the  sympathetic,  and  that  Addison's  disease 
arises  as  part  >>{'  a  general  trophoneurosis.  Such  views  emphasize  vasomotor 
disturbances  and  an  unequal  distribution  of  blood  in  the  body,  whereby  there 

occiiiv-  a   hyperemia    in    the  area   of   the  -|ilaiichnic   nerve   with   anemia   of   the 

peripheral  parts;  but  these  views  are  opposed  by  the  absence  in  many  cases 
of  well  developed  anemia.  I '»et  ween  these  groups  of  op  in  ion-  are  earlier  views 
according  to  which  nothing  but  a  general  cachexia  (which  by  some  is  desig- 
nated a-  a  tubercular  cachexia)  i-  -aid  to  be  the  basis  of  the  clinical  picture. 
The  disease  is  sometimes  designated  a-  an  "anematosis"  (Pepper)  depending 
upon  a  profound  disturbance  of  blood  production,  but   this  view  cannot   be 

accepted    because   of   the   small    number  of   Cases    which    -how    blood    ch;i! 

Main  other  theories  might  be  mentioned. 


222  ADDISON'S  DISEASE 

But  I  must  repeat  that  the  endeavor  to  propound  such  theories  is,  for  the 
present,  not  worth  the  labor.  On  account  of  the  uncertainty  which  still  exists 
regarding  the  function,  not  only  of  the  adrenals  but  also  of  individual  areas  of 
the  sympathetic  nervous  system,  there  is  but  little  hope  of  following  the 
complicated  pathologico-anatomical  changes  which  produce  the  symptoms  of 
the  disease.  I  believe  it.  therefore,  to  be  correct  to  adhere  to  this  view  in  the 
explanation  of  the  pathologic  process:  That  the  disease  depends  upon  a  patho- 
logic modification  or  cessation  of  the  normal  relation  to  the  organism  of  the 
necessary  functions  of  the  adrenals  and  of  the  nerve  areas  which  are  inti- 
mately connected  with  these  structures. 

The  scant  investigations  at  hand  are  naturally  still  open  to  doubt,  and  may 
be  modified  or  rejected  after  later  researches.  Whether,  in  the  future,  we 
must  be  content  with  an  explanation  such  as  has  just  been  given,  or  whether 
we  shall  be  able  to  determine  the  more  minute  pathogenetic  processes  in  Addi- 
son's disease  depends  upon  the  results  of  continued  investigations.  In  my 
opinion,  judging  by  what  has  preceded,  these  researches  must  be  based 
less  upon  physiological  experiment  than  upon  increased  and  minute  histologic 
investigation,  especially  in  the  areas  of  the  nervous  system  that  are  implicated; 
we  also  need  research  in  the  field  of  the  chemistry  of  the  adrenals,  of  the  blood, 
and  of  metabolism.  By  histological  study  the  question  of  the  constancy  of 
a  lesion  of  the  nerves  in  Addison's  disease  will  be  solved ;  by  chemical  research 
the  probable  implication  of  the  adrenals  in  pigmentation  of  the  skin  will  have 
to  be  decided.  For  histological  investigation,  the  atypical  cases  without  dis- 
ease of  the  adrenals  will  be  of  the  greatest  importance.  As  such  cases  are 
particularly  rare,  these  advances  in  our  knowledge  will  be  very  gradual,  and 
it  will  be  all  the  more  necessary,  therefore,  for  us  minutely  to  investigate  each 
available  case  in  the  future. 

*  DIAGNOSIS 

A  few  words  regarding  the  diagnosis  of  Addison's  disease  may  be  added, 
particularly  as  the  view  has  lately  been  expressed  that  diagnosis  is  not  possible 
during  the  life  of  the  patient.  Such  a  view  refers  of  course  only  to  the  deter- 
mination during  life  of  the  pathologico-anatomical  changes  which  are  ex- 
pected in  the  adrenals,  or  (and  this  we  must  emphasize  according  to  our 
experience)  in  their  surrounding  areas,  especially  in  the  sympathetic  nervous 
system.  The  clinical  picture  of  the  disease  in  question,  even  when  it  does 
not  present  itself  in  typical  form,  is  usually  not  difficult  to  recognize.  It  has 
previously  been  stated  that  this  affection  is  very  similar  to  many  other  discol- 
orations  of  the  skin  combined  with  cachexia,  for  instance,  to  certain  forms  of 
tuberculosis,  carcinosis,  malaria,  pellagra,  vagabond's  disease,  and  the  like. 
These  affections,  under  some  circumstances,  may  show  similarity  to  the  Addi- 
son symptom-complex.  But  a  longer  clinical  observation  of  most  of  them 
will  lead  to  a  correct  conclusion,  since  in  these  diseases  (as  has  been  mentioned 
above)  the  pigmentation  differs  by  certain  irregularities,  and  by  the  absence 
of  implication  of  the  mucous  membranes,  from  true  bronzing  of  the  skin, 
and,  further,  because  the  symptoms  directly  referable  to  the  suprarenal  region 


THERAPY  223 

are  absent.  Above  all,  the  correct  etiology  may  usually  be  recognized  in  the 
other  clinical  conditions.  If.  however,  these  pseudo-Addisonian  affections  can 
be  excluded,  and  if  the  true  Addison  symptom-complex  is  present,  we  musl 
remember  the  presence  of  changes  which,  according  to  experience,  are  fre- 
quently present;  viz.,  caseation  of  the  adrenals,  a  presumption  which  may  be 
confirmed  by  the  determination  of  tuberculous  disease  in  other  organs,  par- 
ticularly a  moderately  advanced  pulmonary  tuberculosis.  In  a  similar  man- 
ner, in  a  small  number  of  cases,  secondary  symptoms  which  favor  carcinosis 
or  kindred  affections  may,  perhaps,  be  combined  with  a  palpable  tumor  in  the 
adrenal  region,  this  directing  the  diagnosis  to  a  malignant  growth  of  the 
adrenals.  Only  where  both  these  forms  of  adrenal  disease  are  unlikely  will 
the  assumption  of  any  other  and  rarer  form  of  adrenal  disturbance  be  justi- 
fied, Jn  all  eases  it  must  be  remembered  that,  besides  disease  of  the  adrenals, 
an  affection  of  the  surrounding  nerve  areas,  particularly  of  the  abdominal 
sympathetic  plexus,  with  a  greater  or  less  distribution  to  the  central  nervous 
system,  may  be  present;  that  moreover  under  some  circumstances,  these  dis- 
eases  of  the  nervous  system  may  take  the  place  of  the  affection  of  the  adrenals ; 
and  that,  finally,  in  rare  exceptional  eases,  both  may  be  absent.  That  the 
finding  of  the  latter  cases,  however,  is  not  opposed  to  the  clinical  diagm 
"Addison's  disease,"  T  need  not  reiterate. 

On  the  other  hand,  the  cases  of  profound  adrenal  degeneration  without 
the  symptoms  of  Addison's  disease,  particularly  without  bronzing  of  the  skin 
(which  are  not  very  rare),  will  generally  be  impossible  of  diagnosis.  That 
these  do  not  belong  to  Addison's  disease,  in  the  strict  sense  of  the  term.  1 
have  already  stated.  Lately  it  has  been  proposed  to  differentiate  them  by 
the  term  "adrenal  insufficiency."'  Only  in  instances  in  which  the  disturb- 
ances point  definitely  to  the  adrenal  region,  and  particularly  where  palpation 
-bow-  a  tumor  or  other  abnormal  condition  in  this  area,  can  this  type  of 
disease  of  the  adrenals  be  suspected.  Where  this  is  not  the  case,  the  picture 
of  a  genera]  cachexia  is  present,  a  picture  which,  as  a  rule,  is  not  characteristic 
enough  to  separate  it  from  other  constitutional  disturban 

THERAPY 

The  doubts  which  envelop  the  pathogenesis  of  Addison's  disease  will  natu- 
rally also  appear  in  the  vriews  which  dominate  the  treatment  of  this  affection. 
Accordingly  we  note  from  the  time  at  which  the  clinical  picture  became  known 
up  to  within  the  las!  few  year-  but  few  endeavors  to  adopl  a  specific  or  method- 
ical treatment  of  the  affection,  and  these  few  have  not  been  further  developed. 
Thus,  by  some  observers,  remedies  such  as  faradization,  hydrotherapy,  amy! 
nitrite,  nitroglycerin  (on  account  of  its  action  in  raising  blood-pressure) 
and  transfusion  have  been  employed  and  advised  without  having  obtained 
general  recognition.  In  some  of  these  instances,  and  by  these  methods  of 
treatment,  a  decided  improvement  is  said  to  have  resulted,  and  some  cases 
have  been  reported  even  as  "almosl  cured,"  and  to  have  died  only  during  a 
relap-e.  There  are  intercurrent  improvements  to  which  I  have  already 
ferred  when  discussing  the  spontaj u-  tendency  of  the  disease  to  a  fluctuat- 


224  ADDISON'S   DISEASE 

ing  course.  In  these  remissions  a  cessation  of  all  the  clinical  symptoms  not 
infrequently  precedes  the  fatal  terminal  stage,  but  the  improvement  cannot  be 
looked  upon  as  the  effect  of  treatment.  However,  it  is  quite  likely  that  such 
spontaneous  remissions  may  be  favored  and  increased  by  active  symptomatic 
treatment  and  general  hygiene. 

That  up  to  the  present  time  no  cure  of  a  case  of  Addison's  disease  has 
been  authenticated  has  already  been  remarked.  The  few  cases  which  have 
been  assumed  to  be  such  by  their  observers  are  doubtful  as  regards  the  diag- 
nosis. Under  these  circumstances,  the  opinion  of  Potain,  who  is  said  to  have 
seen  a  case  cured  and  who  believes  that  the  disease  in  one-tenth  of  the  cases 
is  curable,  is  incomprehensible.  Similar  doubts  are  expressed  in  regard  to 
a  case  recently  reported  (by  Oestreich),  which  is  looked  upon  as  an  "  operative 
cure  "  of  Addison's  disease,  and  which  I  shall  briefly  mention :  In  a  woman 
whose  pulmonary  apex  showed  the  symptoms  of  an  old  focus  of  infiltration, 
and  who  suffered  from  marked  cachexia,  there  was  difficulty  in  digestion,  gas- 
tric and  lumbar  pains,  and  a  tumor  the  size  of  a  small  apple  was  found  in  the 
gastric  region.  This  was  removed,  and  after  a  good  recovery  from  the  opera- 
tion the  symptoms  of  the  patient  disappeared,  strength  increased,  and  in  the 
following  nine  months  she  was  looked  upon  as  well.  The  tumor  was  found 
to  be  a  tuberculous,  degenerative  adrenal  organ  surrounded  by  a  fibrinous  cov- 
ering; the  medullary  substance  of  the  organ  was  almost  entirely  destroyed. 
That  in  this  case  extirpation  of  the  tuberculous  adrenal  led  to  recovery  cannot 
be  doubted;  but  unilateral,  adrenal  tuberculosis  with  cachexia  and  gastric 
disturbance  is  not  Addison's  disease;  and  that  the  patient  -without  an  opera- 
tion would  have  succumbed  to  Addison's  disease  is  open  to  doubt. 

Thus,  until  recently,  the  symptomatic  treatment  of  the  clinical  symptoms 
has  been  the  only  therapeutic  indication  in  Addison's  disease,  and  besides 
observation  of  the  gastric  and  intestinal  symptoms  (in  which  we  were  warned 
quite  properly  against  the  use  of  extremely  active  or  drastic  remedies,  as  by 
this  means  uncontrollable  diarrhea  may  be  produced),  on  account  of  the  promi- 
nence of  the  asthenic  phenomena,  the  use  of  tonics  was  the  main  indication. 
Iron  and  arsenic  here  played  an  important  role,  and  I  must  mention  that  in 
the  two  cases  observed  by  me  the  longest  quiescence  of  the  disease  with  transi- 
tory improvement  of  all  the  symptoms,  also  of  the  discoloration  of  the  skin, 
occurred  after  the  continued  use  of  Fowler's  solution  in  large  doses. 

An  advance  occurred  in  the  treatment  of  the  affection  when  the  study  of 
the  internal  secretion  of  certain  organs,  above  all  of  the  so-called  blood-vessel 
glands,  was  combined  with  an  attempt  to  introduce  organotherapy.  In  fact, 
a  malady  such  as  Addison's  disease,  in  which  evidently  in  the  majority  of 
cases  the  main  and  occasionally  the  only  known  pathological  basis  consists  in 
the  destruction  and  gradual  functional  deterioration  of  a  blood-vessel  gland 
necessary  to  life,  appeared  to  be  particularly  suitable  for  the  modern  therapy  of 
compensation.  Theoretic  and  experimental  investigations,  above  all  the  trials 
with  injections  of  suprarenal  extract  in  animals,  already  mentioned  and 
described,  show  the  conspicuous  and  important  actions  of  this  secretion.  I 
shall  only  add  that  in  these  animal  researches  the  value  of  adrenal  therapy 
was  in  part  directly  confirmed :  thus  in  experimental  animals,  after  bilateral 


THERAPY  225 

renal  extirpation,  life  could  be  prolonged  for  twenty-four  hours  by  injections 
of  suprarenal  extract  (Andersson  and  Hultgren).  Moreover,  experience 
proved  that  in  disease  of  the  thyreoid  gland,  which  may  be  looked  upon  as  an 
analogous  condition,  by  a  simple  substitution  therapy,  the  deleterious  conse- 
quences of  the  absence  of  the  thyreoid  could  be  combated,  and  a  fatal  general 
affection,  such  as  myxedema,  could  thus  be  transformed  into  a  harmless  con- 
dition. Therefore,  it  is  not  surprising  that  in  the  last  eight  or  nine  years, 
following  the  English  physicians,  various  investigators  have  attempted  to 
employ  suprarenal  therapy  in  Addison's  disease,  in  which  either  the  gland  in 
substance  or  preparations  obtained  from  the  glands  were  introduced  into  the 
body.  Besides  the  amelioration  or  cure  of  the  affection,  they  hoped  in  this 
manner  to  demonstrate,  more  conclusively  than  by  the  animal  experiments, 
the  direct  dependence  of  the  disease  upon  the  disappearance  of  the  adrenals, 
and  also  to  show  that  the  physiology  and  the  pathology  of  the  adrenals  were 
directly  analogous  to  the  thyreoid  gland  and  athyreoidism. 

unfortunately  the  results  of  suprarenal  treatment  in  Addison's  disease 
have  not  justified  these  hopes.  No  cure  of  the  disease  in  this  way  has  been 
recorded  up  to  the  present  time.  Yet  a  certain  number  of  cases  have  been 
reported  in  which  by  this  treatment  transitory  improvement  followed,  and  was 
so  conspicuous  that  it  could  not  be  disregarded  entirely.  Among  these  cases, 
perhaps  the  most  convincing  are  those  in  which,  after  cessation  of  the  specific 
treatment,  an  ayyraraliun  of  the  general  condition  occurred,  and.  eventually, 
pigmentation  of  the  skin  followed;  of  these,  two  are  particularly  worthy  of 
mention : 

Thus  Schilling  (1897)  reports  the  case  of  a  boy.  aged  fifteen,  who  was 
ill  for  two  years  and  showed  quite  decided  bronzing.  For  three  months  raw 
adrenal  substance  was  administered  to  him  (a  fresh  gland  from  a  sheep  or 
lamb  daily).  During  this  time  an  almost  complete  disappearance  of  the 
abnormal  pigmental  ion  occurred  (only  a  slight  discoloration  upon  the  mucous 
membrane  of  the  mouth  remaining)  and  an  increase  in  strength  and  of  weight 
(33  pounds)  so  that  he  was  looked  upon  as  almost  well.  After  a  three  months' 
cessation  of  the  treatment,  and  following  sudden  symptoms  of  intoxication, 
death  occurred  (perhaps  in  consequence  of  a  beginning  pneumonia).  The 
adrenals  were  contracted   almosl    to  cicatrices,  and  permeated   by  caseous   foci. 

More  striking,  perhaps,  is  the  case  observed  by  Edel  (1900):  A  locksmith, 
aged  thirty-three,  in  whom  the  symptoms  of  rapidly  increasing  weakness  and 
bronzing,  particularly  of  the  face,  dorsum  of  the  hands,  and  penis,  had  existed 
for  six  months  without  showing  any  remission.  Suprarenal  tablets  were 
administered  (one  gram  each,  two  given  twice  daily),  and  after  only  two  to 

thr lavs  his  strength  began  to  increase,  bo  that  after  fourteen  days  he  was 

able  to  return  to  work:  moreover,  the  bronzed  areas  of  the  skin  began  to 
improve  from  the  third  day  of  treatment,  and  live  weeks  later  hands,  face 

and  penis,  with  the  exception  of  isolated  area-,  were  again  of  a  normal  color. 
After  a  month  and  a  half  of  improvement,  tubercular  meningitis  set  in  and 
caused  death  in  seven  days.  From  the  beginning  of  this  complication  the 
adrenal   tablets  had   been   -topped,   the  bronzing  reappeared,  and   a   short    time 

prior  to  death  had  almost  completely  returned.     The  autopsy  showed,  besides 

10 


226  ADDISON'S  DISEASE 

distributed  caseation  of  the  glands,  a  tuberculous  nodule  in  only  the  right 
adrenal,  while  the  solar  plexus  and  the  semilunar  ganglion  were  embedded  in 
callous  connective  tissue. 

In  the  study  of  such  examples  the  previously  mentioned  tendency  of  cer- 
tain cases  of  Addison's  disease  to  spontaneous  remission  with  consequent-  fatal 
exacerbation  is  to  be  remembered.  But  it  must  be  admitted  that  here  the 
rapidity  and  the  complete  amelioration  of  the  symptoms  appears  to  be  out  of 
proportion  with  what  is  observed  in  the  spontaneous  course  of  the  disease. 
Particularly,  in  the  second  case,  the  complete  recurrence  in  a  few  days  of  the 
dark  bronzing  of  the  sTcin  can  only  he  understood  by  assuming  a  preceding 
artificial  modification  of  the  pigment  metabolism  of  the  body.  It  appears 
that  these  two  cases,  and  a  few  similar  ones,  are  sufficient  to  prove  the  possi- 
bility of  a  favorable  influence  upon  the  principal  symptoms  of  Addison's  dis- 
ease by  the  artificial  introduction  of  suprarenal  substance. 

It  is  true  that  we  have  records  of  quite  a  number  of  cases  opposed  to  these — 
cases  in  which  suprarenal  treatment  had  no  influence  upon  bronzing  of  the 
skin,  nor  upon  the  general  symptoms.  And  from  the  reports  at  hand  I  believe 
that  the  number  of  these  negative  cases  is  at  least  equal  to  those  in  which 
positive  results  have  been  obtained.  Sometimes  indeed  a  direct  aggravation 
of  the  symptoms  has  been  noted  from  the  beginning  of  this  treatment.  Nor 
has  it  been  possible  to  prove  by  chemistry  that  metabolism  in  the  organism 
is  decidedly  influenced  by  the  introduction  of  adrenal  substance.  For  even 
though  one  investigator  (Pickardt),  after  a  nine  days'  research  in  metabo- 
lism in  a  case  of  Addison's  disease,  during  which  time  suprarenal  tablets 
were  administered,  found  an  increase  of  albumin  decomposition,  in  an  analo- 
gous research  by  another  investigator  (Senator),  nothing  abnormal  could  be 
determined.  In  the  case  of  two  dogs  who  were  fed  with  adrenals  (with  the 
raw  gland  as  well  as  with  the  glandular  extract)  similar  experiments  showed 
no  decided  change  of  the  nitrogen  balance  (Blum). 

Perhaps  the  form  and  amount  in  which  the  adrenal  substance  is  adminis- 
tered is  important  for  its  supplementary  action.  Apart  from  a  few  unsuc- 
cessful or  disastrous  investigations  with  the  implantation  of  animal  adrenals 
under  the  skin,  the  glands  have  been  administered  in  a  natural  condition  (as' 
fresh  as  possible),  usually  chopped  up  with  necessary  additions.  They  have 
been  occasionally  given  in  a  dry  condition,  as  adrenal  powder,  but  in  most 
cases  they  have  been  used  as  extract,  which  in  rare  cases  has  been  subcutane- 
ously  injected,  but  has  generally  been  given  internally  in  the  form  of  adrenal 
tablets  (particularly  in  England,  but  also  in  Germany  and  other  countries). 
The  doses  administered  varied  according  to  the  reports,  with  the  fresh  adrenal 
gland,  from  one  to  two  glands  daily;  with  the  extracts,  an  amount  corre- 
sponding to  0.2 — 1.0  of  the  dried  glandular  substance.  It  will  be  noted  that 
the  best  method  of  introducing  the  glandular  substance  has  not  been  definite! v 
determined.  Many  further  observations  will  be  necessary  to  decide  this. 
The  opinion  expressed  by  some  authors  (for  example,  by  Lewandowsky)  that 
the  administration  of  the  raw  glandular  substance  is  more  effective  than  the 
exhibition  of  the  extract  appears  to  be  confirmed  by  a  number  of  clinical 
histories.     But  it  must  be  pointed  out  that  in  the  second  of  the  cases  men- 


THERAPY  227 

tioned  above  the  conspicuous  intercurrent  improvement  occurred  after  the  use 
of  adrenal  tablets.  Whether  an  intravenous  injection  in  man  of  suprarenal 
extract,  which  has  been  advised,  will  produce  a-more  intense  action  than  other 
methods,  and  whether  it  will  not  also  produce  dangerous  symptoms,  appears 
to  be  questionable. 

That  the  results  by  means  of  adrenal  treatment  in  Addison's  disease  are 
no  more  definite  and  gratifying  than  those  mentioned  above  is  not  surprising, 
nor  can  they  be  looked  upon  as  final.  For,  in  the  first  place,  the  number  of 
investigations  is  much  too  small  to  determine  this  therapeutic  question.  I 
estimate  the  number  of  cases  that  have  been  accurately  reported  as  much  less 
than  100;  and  in  mosi  of  these  it  must  be  remembered  that  there  was  oppor- 
tunity for  suprarenal  treatment  only  for  a  short  time,  or  only  very  late  in  the 
course  of  the  disease,  so  that  the  condition  was  an  unfavorable  one  for  therapeu- 
tic results.  Therefore  a  Long  continuance  of  observations  will  he  necessary 
before  a  definite  opinion  can  he  given  regarding  the  value  of  organotherapy  in 
Addison's  disease,  and  to  decide  whether  the  apparent  favorable  results  in 
individual  cases  will  be  guaranteed  by  further  observation. 

But  even  if  organo-therapeutic  results  should  not  improve  with  increasing 
experience,  this  circumstance  cannot  be  used  to  nullify  the  importance  of 
the  adrenal  function  in  the  pathogenesis  of  Addison's  disease.  The  thera- 
peutic introduction  of  adrenals  from  animals,  or  of  extracts  obtained  from 
these,  can  only  substitute  in  a  very  feeble  way  for  the  secretion  furnished  by 
the  living  gland  in  the  human  organism.  Action  similar  to  that  which  is 
exerted  directly  by  the  adrenals  upon  the  fluids  of  the  body  can  hardly  be 
expected  from  the  peripheral  absorption  (through  stomach,  skin,  etc.)  of  the 
finished  product-,  especially  since  the  latter,  as  all  physiologico-chemical  inves- 
tigations have  shown,  are  subjeel  to  greal  destruction  in  the  tissues  of  the 
body.  Comparison  with  the  remarkable  action  of  the  extract  of  thyreoid 
gland  which,  even  in  the  iir.-t  investigations  of  substitution  therapy  was  shown 
to  cure  myxedema,  should  not  lead  as  to  expect  similarly  easy  and  surprising 
results  in  all  analogous  investigations  (even  although  they  appear  to  be  patho- 
genetically  well  founded).  Bince  the  physiologic  and  pathologic  condition-  in 
many  other  organs  are  certainly  much  more  complicated  than  in  the  case  of 

the  thyreoid   -land  and    its   functions. 

A-  regards  the  influence  of  organotherapy  in  Addison's  disease,  we,  must 
content  ourselves  for  the  present  with  stating  that  the  experiences  which  have 
been  gathered  <"'<■  not  sufficient  In  permit  "  conclusion.  They  are  also  insuffi- 
cienl  to  determine  the  likelihood  of  improvemenl  or  cure,  or  to  decide  theo- 
retically whether  or  not  the  artificial  introduction  of  adrenal  secretion  is  a 
proof  of  the  adrenal  theory  in  Addison's  disease.  Hut  neither  do  the  reports 
at  hand  require  thai  we  should  cease  to  hope  that  further  and  more  exact 
therapeutic  investigations  will  furnish  better  results. 

Prom  this,  future  observers  may  learn  the  practical  lesson  to  test  the 
adrenal  treatment  of  Addison's  disease  upon  every  opportunity.  If  we  begin 
the  treatmeni  in  individual  cases  a-  early  as  possible,  and  compare  the  influ- 
ence of  the  various  modes  of  administration,  we  -hall  gradually  be  able  to 
determine  what  to  expect   from  this  method  of  treatment,  ami  to  recognize 


228  ADDISON'S  DISEASE 

whether  there  is  any  well  founded  hope  of  successful  substitution  therapy  in 
Addison's  disease.  As  in  the  pursuit  of  pathologico-anatomical  knowledge 
of  the  disease,  so  here  a  long  time  may  elapse,  as  cases  of  the  disease  which 
are  especially  suitable  for  favorable  treatment  are  very  rare  in  almost  all 
countries. 

Thus  we  see  that  in  the  realm  of  practical  therapy  in  Addison's  disease 
much  is  still  obscure  and  much  must  be  left  for  further  investigation. 

If  we  now  return  to  the  question  at  the  beginning  of  this  article,  whether 
according  to  present  knowledge  we  may  declare  that  Addison  s  disease  may  be 
explained  by  an  absence  of  the  adrenal  function,  we  must  give  the  answer 
already  indicated  more  than  once,  that  for  several  reasons  this  is  impossible. 
The  numerous  experiments  which  have  been  carried  out  in  clinical,  anatomical, 
physiological,  chemical  and  therapeutic  realms  in  the  last  half  century  to 
determine  the  basis  of  the  disease  have  given  us  much  knowledge  regarding  the 
clinical  picture  as  well  as  in  regard  to  many  properties  of  the  adrenals.  But, 
as  we  have  seen,  important  links  are  absent  for  the  explanation  of  Addison's 
disease  as  an  affection  of  the  adrenals  alone.  Hence,  in  disease  of  the  gland 
in  combination  with  that  of  other  organs,  particularly  of  parts  of  the  nervous 
system,  it  now  appears  impossible  to  find  this  explanation  without  separating 
the  roles  of  these  parts  in  the  development  of  the  definite  clinical  symptoms. 
This  conception  will  not  appear  strange  to  those  who  have  endeavored  to 
explain  the  disease  as  a  physiologico-chemical  consequence  of  adrenal  disease; 
and  I  believe  it  to  be  more  satisfactory  than  the  subjugation  of  the  pathologic 
process  to  a  restricted  theory  which,  at  least  for  the  present,  leaves  several 
phases  unexplained.  Whether  this  view  will  be  accepted  in  the  future,  or 
whether  the  adrenal  theory  in  a  purer  form  will  be  found  sufficient  for  the 
explanation  of  the  disease,  will  depend  upon  the  results  of  future  experience 
and  investigation.  That  these  researches,  together  with  our  therapeutic  en- 
deavors, will  in  my  opinion  aid  in  the  further  explanation  of  the  disease  upon 
a  pathologico-anatomical  and  also  upon  a  chemical  basis  has  already  been 
indicated.  Thus  continued  investigations  in  the  interesting  clinical  picture 
of  Addison's  disease,  and  the  elaboration  of  the  previous  observations,  are 
bequeathed  to  the  next  decades  of  the  new  century  as  an  object  worthy  of  their 
labors. 


ACROMEGALIA 

By    C.    BENDA,    Berlin 

The  erroneous  idea  that  the  gigantic  is  to  be  looked  upon  as  an  expression 
of  prehistoric  times — primordial — is  firmly  rooted  in  the  human  mind. 
When  we  think  of  the  seas  and  forests  primeval  as  inhabited  by  monsters 
like  the  plesiosaurus  and  the  megatherium  we  readily  conclude  that  a  primor- 
dial race  of  gigantic  people  must  have  represented  the  survivors  of  the  animal 
kingdom  who  vanquished  these  leviathans.  We  are  content  with  the  role  of 
dwarfed  epigones,  and  in  the  specimens  of  unusual  size  occasionally  seen  we 
acclaim  the  revival  of  this  primordial  power.  Science  has  proven  these  fan- 
tasies to  be  incorrect.  We  can  prove,  or  at  least  infer,  that  prior  to  these 
giant  beasts,  as  well  as  to-day,  there  existed  prolific  races  of  smaller  beings. 
Prominent  scientists  assume  that  the  original  forms  of  the  vertebrate  animals 
were  dwarfed  forms.  Nothing  conflicts  with  this  hypothesis,  and  much 
favors  the  probability  that  the  apelike  proanthropos  also,  and  some  at  Least 
of  the  earliest  races  of  man.  were  dwarfs,  even  though  other  primordial  races 
may  have  early  attained  a  larger  structural  development.  Thus  our  views 
regarding  giants  have  been  fundamentally  changed,  since  it  is  unlikely  that 
giants  are  to  be  considered  as  atavistic  or  primordial  type-.  In  the  year  1872, 
Carl  v.  Langer  firsl  proved  by  careful  studies  that  besides  a  normal  form  of 
giant  skulls  a  pathologic  one  may  be  distinguished.  To-day  the  opinion  is 
expressed  that  giani  growth  is  commonly  the  resuH  of  a  pathologic  pro< 

This  change  of  conception  is  intimately  associated  with  our  increasing 
knowledge  of  thai  process  of  pathologic  growth  which  is  the  subjed  of 
this  articli — acromegalia.  The  investigations  of  Pierre  Marie  in  the  year 
188<>  are  to  be  regarded  a-  the  foundation  for  this  knowledge.  Although  cases 
of  the  disease  bad  been  observed  prior  to  this  time  and  to  some  exteni  well 
described,  for  instance,  by  the  Italian  Verga,  it  was,  as  Sternberg  says,  the 
labors  of  the  French  investigator  that  introduced  the  disease  into  the  clinic 
from  medical  monstrosity  and  curio  cabinet-.  Marie  characterized  the  affec- 
tion  by  means  of  the  peculiar  symptoms  which  had   al-o  been   noted   by  other 

observers,  and  of  which  now  one.  now  another,  proved  mo-t  interesting.  II«1 
also  worked  out  the  principal  clues  for  tin-  differentiation  of  this  process  from 
other  affections  which  had  some  symptoms  in  common  with  it.  Marie  deserves 
-till  further  credit  for  giving  to  the  disease  it-  characteristic,  euphonious,  and 
easily  remembered  name,  for  we  mu-t  remember  how  readily  the  human  mind 
adhere-    to    a     -(heme,    and     by     adopting    a     distinctive    name    grasps     the 

conception    which    the   name  embodies.      Nevertheless    there    is    an    impor- 


230  ACROMEGALIA 

tant  point,  not  brought  out  in  the  name,  which  must  be  borne  in  mind 
if  the  pathologic  process  and  the  autopsy  finding  are  to  be  accurately  remem- 
bered :  It  is  not  the  size  of  the  extremities  which  represents  the  most  striking 
symptom  of  the  disease,  as  might  be  concluded  from  the  name;  it  is  the 
enlargement,  the  abnormal,  disproportionate  growth  of  these  parts.  If 
Cyrano  de  Bergerac,  besides  his  celebrated  nose,  had  had  large  hands  and 
feet,  regarding  which  history  probably  gives  no  reliable  reports,  this  would 
not  have  been  a  sufficient  reason  for  calling  him  acromegalic,  provided  he  had 
had  these  deformities  from  birth,  or  by  heredity.  In  contradistinction  to  some 
descriptions  (even  very  recent  ones)  of  "unquestioned"  acromegalic  symp- 
toms in  the  bony  skeleton,  it  must  again  be  pointed  out  that  the  characteristic 
symptom  of  the  disease  is  not  the  unusual  form  of  certain  parts  but  their 
advancing  change,  and  that  in  any  case  in  which  anamnestic  and  clinical 
data  in  regard  to  this  symptom  were  absent  only  the  existence  of  all  the  other 
factors  and  the  resemblance  to  the  picture  of  acromegalia  can  be  considered 
presumptive  evidence.  This  is  a  concession  to  clinical  medicine  which  re- 
quires a  certain  amount  of  self-denial  on  the  part  of  the  pathological  anato- 
mist, but  the  historical  honor  must  in  this  case  be  accorded  to  the  clinician 
who  founded  the  conception  of  the  disease. 

By  Pierre  Marie's  pioneer  labors,  by  the  long  series  of  his  thorough  in- 
vestigations and  by  those  of  his  pupils,  as  well  as  by  a  great  number  of  clinical 
and  pathological  researches  in  which  the  most  prominent  scientists  have  taken 
part,  such  an  exhaustive  description  of  the  disease  has  been  given  that  it 
may  almost  be  regarded  as  complete.  Excellent  comprehensive  treatises, 
among  which  those  of  M.  Sternberg  are  to  placed  in  the  front  rank,  have  dis- 
seminated this  knowledge  throughout  the  medical  profession. 

ETIOLOGY 

The  tendency  to  this  disease  is  an  unfortunate  prerogative  of  early  matur- 
ity; one-half  of  all  the  known  cases  develop  in  the  third  decade  of  life.  Less 
frequently  cases  occur  between  the  thirtieth  and  fortieth  years,  and  a  few 
begin  later;  rarely  has  an  onset  before  the  twentieth  year  been  observed. 
Special  stress  must  be  laid  upon  the  point  that  the  disease,  although  usually 
beginning  after  the  body  has  attained  its  normal  growth,  nevertheless  occurs 
at  a  time  of  life  when  there  is  still  decided  plasticity  of  the  body,  and  the 
form  thus  presented  must  be  separated  from  that  of  the  true  senile  period. 

Both  sexes  are  affected  to  the  same  extent,  but  in  the  cases  that  begin  late 
a  decided  predominance  of  women  has  been  noted.  The  disease  is  quite  rare. 
I  believe  that,  including  the  four  typical  cases  upon  which  I  held  an  autopsy, 
I  have  had  more  cases  than  any  other  pathologist.  These  are  included  in 
about  8,000  autopsies  which  I  have  seen  in  a  service  of  eight  years  in  the 
Urban  Berlin  Hospital;  curiously,  three  of  these  cases  occurred  in  a  period  of 
thirteen  months  from  March,  189G,  to  April,  1897,  and  only  one  occurred 
before  or  after  this  period. 

As  may  be  seen  from  the  previously  mentioned  observations  of  v.  Langer, 
there  are  obvious  relations  between  acromegalia  and  giant  growth  since  it 


SYMPTOMS  231 

appears  that  acromegalia  most  frequently  attacks  individuals  characterized 
already  by  great  bodily  size.  According  to  Sternberg  20  per  cent,  of  the 
"  giants  "  are  attacked  by  acromegalia.  Among  my  four  cases  two  were  above 
medium  size.  But,  as  is  noticeable  from  the  figures,  the  relation  is  not  a 
necessary  one.  At  this  point  I  should  like  to  call  attention  to  the  fact  that 
in  the  skeleton  of  a  dwarf  which  is  in  the  Berlin  Pathological  Museum,  and 
which  I  had  an  opportunity  of  examining  through  the  kindness  of  Professor 
Waldeyer,  I  l'ound  suspicious  acromegalic  stigmata,  so  that,  with  all  due  regard 
to  what  has  been  expressed  above,  I  may  presume  that  even  dwarfs  are  not 
exempt  from  the  disease. 

The  cause  of  the  disease  is  enveloped  in  obscurity.  Of  course  trauma  and 
psychical  emotion,  as  in  all  diseases  which  involve  the  nervous  system,  are 
mentioned  as  starting  points  by  the  patients  and  their  relatives,  and  are  sug- 
gested as  causes  of  the  affection. 

SYMPTOMS 

The  onset  of  the  disease  is  accompanied  by  very  various  neuropathic  phe- 
nomena. There  are  reports  of  extreme  lassitude,  of  drawing  pains  and  pares- 
thesia in  the  head  and  in  the  extremities;  in  short,  mild  symptoms  such  as 
almost  every  patient,  whatever  hi-  disease,  will  admit  if  they  are  suggested  to 
him,  such  also  as  almost  any  healthy  person  will  also  acknowledge.  Of  impor- 
tance in  women  is  the  invariable  cessation  of  menstruation,  and  in  some  males 
the  appearance  of  impotence. 

The  peculiar  changes,  as  a  rule,  are  first  noticeable  in  the  face.  A  distor- 
tion of  the  feature-  occurs  which  renders  the  patient  unrecognizable  to  his 
nearest  relative-,  and  this  in  a  few  cases  can  also  be  objectively  shown  by 
photographs  taken  prior  to  the  disease  if  the  pictures  and  the  patient  are 
brought  together  for  comparison.  T  must  further  take  this  opportunity  to 
warn  physicians  against  photographs  of  acromegalic  patients.  I  regret  that 
I  musl  sow  the  seed-;  of  doubt  in  what  the  laity  believe  to  he  the  absolute  art 
of  photography,  hut  I  am  a  photographer  myself,  and  I  know  how  the  products 
of  this  art  are  attained.  Besides  pathologic  acromegalia,  there  i-  also  (as  I 
must  reveal)  an  artificial  one.  which  in  portraits  by  novice-  in  photography 
i-  almost  epidemic.  This  always  occurs  when  a  picture  is  taken  of  the  entire 
Bitting  figure,  full  face,  with  arms  and  legs  extended.  This  depends  upon  a 
simple  perspective  effect  due  to  the  use  of  photographic  objectives  of  -bort 
focus,  and  to  our  habit  of  placing  the  objeel  at  n  very  -hurt  distance  from 
the  camera  as  is  necessary  to  obtain  large  pictures.  The  lir-t  cause  of  this 
faulty  perspective  i-  the  misplacement  of  the  object,  which  i-  seen  in  almost  all 
pictures  of  acromegalics  that  are  known  to  me.  In  such  pictures  full  face 
reproduction,  similar  to  that  of  the  statues  of  Egyptian  kings,  ha-  almosl 
become  typical.     How  far  the  other  effects  of  this  faulty  perspective  extend 

can  only  he  determined  by  picture-  in  which  the  distortion,  even  of  a  single 
extremity,  is  recognizable  at  once,  a-  in  a  picture  in  my  possession,  in  which 
the  extended  greal   toe-  are  almo-t   a-  broad  a-  all   the  re<t   of  the   foot.      The 

photographer  has  unconsciously  intensified  the  impression  of  the  abnormal- 


232  ACROMEGALIA 

ity  that  is  to  be  depicted ;  if  he  had  used  a  normal  hand  as  a  comparison  for 
the  pathologic  condition  he  would  have  perceived  that  the  former,  to  make 
the  comparison  possible,  would  have  to  be  brought  the  same  distance  from 
his  apparatus  as  the  latter,  and  not  be  left  perhaps  half  a  yard  behind,  as  was 
the  case  in  the  picture  portraying  the  condition  of  the  feet. 

But,  to  return  from  this  digression,  aside  from  this  little  photographic 
trick,  a  practised  eye  is  not  necessary  to  note  in  the  advanced  stages  of  the 
disease  the  very  characteristic  condition  of  the  face.  The  prominent  super- 
ciliary ridge,  with  the  bushy  eyebrows  which  occasionally  almost  meet  in  the 
median  line,  gives  the  face  a  threatening  expression ;  the  swollen  lips,  the 
very  prominent  zygomatic  arch  and  the  lower  jaw  give  a  somewhat  bestial  ex- 
pression, and  the  enormous  nose  with  its  grim  humor  forms  the  only  redeem- 
ing feature. 

A  similar  and  progressive  deformity  in  the  extremities  gradually  becomes 
noticeable.  The  feet  become  plump,  larger;  and  broader,  and  the  hand  which 
is  deformed  till  it  is  like  a  bear's  paw  appears  especially  conspicuous.  This 
impression  is  further  increased  by  the  comparative  slenderness  of  the  lower 
arm.  The  X-ray  picture  shows  that  the  bones  are  covered  with  exostoses; 
these  are  particularly  noticeable  at  the  end  phalanges  of  the  fingers  and  toes. 
According  to  Pierre  Marie  two  forms  of  alteration  of  the  hand  are  to  be 
differentiated,  one  of  which  consists  in  a  general  enlargement,  the  other  in  a 
thickening  of  the  bones  of  the  hand.  In  the  latter  the  exostoses  are  more 
prominent. 

Regarding  the  enlargement  of  the  internal  organs,  one  above  all  others 
becomes  clinically  conspicuous,  and  must  be  counted  among  the  most  impor- 
tant and  constant  symptoms  of  the  disease — I  mean  the  tongue,  which 
may  assume  extraordinary  dimensions.  In  some  cases  closing  of  the  mouth 
is  no  longer  possible.  Enlargement  of  the  thyreoid  gland  is  often  rec- 
ognizable. 

Of  great  importance,  but  not  always  present,  are  the  symptoms  which 
point  to  a  tumor-like  enlargement  of  the  hypophysis.  These  symptoms  are 
principally  those  of  a  basal  cerebral  tumor,  but  from  the  description  of  the 
autopsy  finding  we  shall  readily  understand  that  these  symptoms  need  not 
occur,  even  in  very  large  tumors  of  the  hypophysis,  so  long  as  the  tumor  does 
not  invade  the  cavity  of  the  skull.  In  many  cases  the  symptoms  in  question 
are,  however,  well  developed.  They  consist,  first,  in  severe  headache  which 
occurs  in  paroxysms,  vertigo,  vomiting,  decrease  of  intelligence  and,  in  par- 
ticular, somnolence.  The  direct  pressure  of  the  tumor  of  the  hypophysis  acts 
most  constantly  upon  the  optic  nerves,  or  upon  the  optic  chiasm,  and  shows 
itself  in  hemianopsia,  amblyopia  even  to  amaurosis,  due  to  atrophy  of  the 
stretched  and  compressed  optic  nerves.  More  rarely  the  muscles  of  the  eye 
are  implicated,  especially  those  supplied  by  the  oculomotor  nerve.  At  this 
point  I  must  also  mention  exophthalmos  which  has  been  observed  in  many 
cases,  and  which  is  usually  referred  partly  to  the  change  in  the  bones  of 
the  orbit,  and  partly  to  enlargement  of  the  bulbus  oculi.  I  believe,  how- 
ever, that  the  fact  that  acromegalic  exophthalmos  occurs  periodically  may  best 
be  explained  by  the  assumption  that  it  is  not  due  to  organic  changes  in  the 


SYMPTOMS  233 

cavity  of  the  eye,  but  to  stasis  in  the  sinus  cavernosus,  as  might  readily  occur 
from  the  pressure  of  a  hypophyseal  tumor. 

How  many  of  the  general  nervous  disturbances  are  to  be  referred  to  the 
tumor,  and  how  many  to  an  independent  disease  of  the  nerves  cannot  be  accu- 
rately determined.  But  among  other  symptoms  I  must  here  refer  to  the 
prominence  of  general  nervous  phenomena,  such  as  pains,  weakness,  sensa- 
tions of  heat  and  the  like.  An  important  role  is  played  by  increased  secre- 
tion of  sweat,  polydipsia,  and  polyuria,  which  in  many  cases  are  probably 
the  sign  of  a  co-existing  diabetes.  Occasionally,  however,  they  certainly 
occur  without  this  condition.  In  the  further  course  of  the  disease  a  conspicu- 
ous loss  of  strength  is  observed,  and  nephritis  and  myocarditis  often  super- 
vene, so  that  we  find  the  picture  of  a  severe  general  intoxication.  Death  results 
in  such  cases  either  from  paralysis  of  the  heart  or  from  bronchopneumonia. 
A  remarkable  and  frequent  complication  of  the  disease  is  diabetes,  which, 
for  example,  occurred  in  two  of  the  lour  cases  observed  in  the  Urban  Hos- 
pital, and  in  one  of  the  patients  was  the  cause  of  death  by  coma.  It  is  ques- 
tionable whether  the  diabetes  of  acromegalics  is  to  be  ascribed  to  the  pre- 
viously mentioned  symptoms  of  intoxication,  or  whether  it  is  directly  due  to 
the  tumor  of  the  hypophysis.  I  incline  to  the  latter  view,  for  in  the  two 
cases  in  which  the  largest  tumors  of  the  hypophysis  were  found  by  us  it  was 
present,  and  disease  of  the  pancreas  was  absent.  Xot  infrequently  the  tumor 
of  the  hypophysis  causes  death  by  edema  of  the  brain.  Finally,  in  a  disease 
which  runs  such  a  slow  course  it  is  not  remarkable  that  intercurrent  affec- 
tion- in  no  way  related  to  the  main  disease  frequently  cause  death.  For 
example,  in  one  ..f  our  cases  a  perforating  peritonitis,  complicating  cancer  of 
tin-  stomach,  led  to  the  fatal  issue. 

Tlir  symptoms  most  dangerous  to  life  are  the  immediate  effects  of  pres- 
sure from  the  tumor  of  the  hypophysis,  and  those  which  presenl  the  general 
symptoms  of  intoxication.  This  is  favored,  as  I  may  mention  here,  from 
a  clinical  standpoint,  by  the  great  importance  of  disease  of  the  pituitary 
body,  ami  also  by  the  fact  that  in  all  the  eases  mentioned  in  literature  in 
which  death  occurred  in  a  shorl  time  without  any  intercurrent  affections, 
the  phenomena  of  the  tumor  of  the  hypophysis  were  mo-l  prominent  in  the 
clinical  picture,  ami  the  autopsy  always  showed  an  extremely  large  tumor. 
Even  though  one  may  not  agree  with  Sternberg's  view  that  these  cases  arc  due 
p,  a  Bpecial  type  of  tumor  (see  below  in  the  account  of  investigations  by 
Hanau  and  myself),  the  claim  of  Sternberg  musl  be  recognized  that  these 

cases  arc  to  he  differentiated  a-  a  "  malignant  "'  form  of  acromegalia.     My  only 

objection  is  thai  Sternberg  defines  this  differentiation  by  such  an  arbitrary 

mark — the  duration   of   the   disease    for    four   year-.      1    do   m.|    doubt    that    at 

lea-t  one  ..f  our  cases,  the  case  of  A.  Frankel.  who  after  sis  years  succumbed  to 
the  disease  without  complications,  musi  also  he  included  in  this  "  malignant  *' 
frroup.  Another  of  mir  cases  of  the  same  duration  would  also  he  included 
here  if  \\i<  assume  the  fatal  diabetes  which  existed  in  this  case  to  be  a  symptom 
of  the  tumor  of  the  hypophysis,  a-  1  unquestionably  do.  it  i-  somewhal  arbi- 
trary, therefore,  to  divide  the  other  cases,  a-  proposed  by  Sternberg,  into  an 

'•ordinary"  and   a   "benign"    form,   a-   they    may    la-t    thirty,   or  even    up   to 


234  ACROMEGALIA 

fifty,  years.  It  appears  to  me  more  rational  to  regard  as  malignant  or  acute 
all  cases  which  pursue  an  uncomplicated  and  progressive  course  leading  to 
death.  In  this  type  of  disease  the  cases  on  record  show  that  a  duration  of 
about  six  years  is  the  rule.  It  is  best  to  regard  as  benign  or  chronic  all  cases 
in  which  death  is  probably  caused  not  by  the  acromegalia  but  by  complications 
which  are  not  connected,  or  but  slightly  connected  with  the  main  disease. 

PATHOLOGY 

A  somewhat  wider,  but  by  no  means  complete  knowledge  of  the  nature  of 
this  remarkable  disease  has  been  obtained  by  autopsies  and  microscopic  investi- 
gations, of  which  quite  a  number  are  already  at  hand.  Beginning  with  the 
skeleton,  we  shall  first  direct  our  attention  to  the  bones  of  the  hands  and  feet, 
which  form  the  nucleus  of  the  astonishing  anomalies  of  growth  that  appear 
during  life.  It  is  unquestionable  that  the  bones  in  many  of  the  cases  that 
have  been  described  showed  great  enlargement.  A  case  lately  reported  by 
0.  Israel  is  a  prominent  example  of  this  kind.  I  believe,  however,  that  in 
most  cases  a  sensation  of  slight  disappointment  cannot  be  suppressed  when 
the  skeleton  of  the  hand  or  foot  is  compared  with  our  recollection,  or,  better. 
with  a  plaster  cast  of  the  fleshy  member.  Above  all  Ave  are  then  convinced 
that  the  most  prominent  disturbance  of  proportions  in  many  cases  has  almost 
disappeared,  and  only  minute  comparison  with  normal  skeletons  will  enable 
us  to  note  the  abnormalities.  The  flattening  and  irregularities  of  the  end 
phalanges,  which  at  the  onset  attract  attention,  as  Sternberg  correctly  states, 
are  but  slightly  different  from  the  normal  skeleton,  but  it  appears  to  me  that 
in  acromegalia,  they  are  found  somewhat  more  constantly  than  in  normal 
skeletons.  In  a  foot  in  our  collection  the  second  phalanx  of  all  the  toes  from 
the  second  to  the  fifth  is  somewhat  elongated.  Otherwise,  however,  only  the 
insertions  of  the  muscles  and  tendons  are  roughened,  thickened  and  covered 
with  osseous  proliferations.  It  is  these  which  at  first  sight  give  the  impres- 
sion of  gross  deformity.  Upon  minute  investigation  we  discover  smaller  exos- 
toses, irregular  porosities  of  the  cortical  layer,  bony  outgrowths  upon  the  ends 
of  the  joints  and  the  like,  but  we  must  admit  that  even  all  of  these  collectively 
cannot  produce  the  picture  of  the  "  bear's  paw,"  as  we  see  it  in  life.  The 
same  impression  is  conveyed  on  examining  the  long  tubular  bones  of  the  ex- 
tremities, as  well  as  those  of  the  trunk.  Everywhere  the  important  point  is 
the  decided  roughness  of  the  insertion  of  muscles  which  have  proliferated; 
otherwise  the  hones  show  only  moderate  change  in  form.  As  an  exception  I 
must  mention  the  clavicle,  which  in  most  cases  of  acromegalia  shows  a  decided 
increase  in  bulk.  But  we  must  not  permit  ourselves  to  be  led  astray  by  occa- 
sional investigations  of  individual  bones.  One  femur  in  our  collection  shows 
enormous  thickness,  but  it  belongs  to  Stadelmann's  case,  and  must  be  correctly 
looked  upon  as  a  combination  of  acromegalia  with  gigantism,  and  may  be 
entirely  independent  of  the  former  disease. 

The  vertebral  column  occasionally  shows  ankylosis  of  the  vertebral  bodies 
by  bony  bridges,  but  the  commonest  lesions  are  the  hyperostoses  and  exostoses 
of  the  vertebral  processes,  which  perhaps  form  the  main  substratum  of  the 


PATHOLOGY  235 

frequently  observed  kyphosis  of  acromegalics,  unless,  as  Arnold  supposes,  it  is 
habitual  and  duo  To  the  weight  of  the  head. 

The  lesions  in  the  bony  skull  are  of  quite  different  significance.  The  roof 
of  the  skull  shows  no  gross  changes  except  early  obliteration  of  the  sutures 
and  flat  exostoses.  Upon  the  base  of  the  skull  the  sphenoid  bone  is  of  chief 
interest,  and  always  shows  more  or  less  deformity  duo  to  the  tumor  of  the 
hypophysis.  Its  upper  surface  almost  always  shows  a  widening  of  the  fovea 
hypophyseos,  with  disappearance  of  the  dorsum  sellse.  In  other  cases  the 
floor  is  decidedly  deepened  and  eroded,  so  that  the  sinus  of  the  sphenoid 
bone  is  laid  bare  above.  In  several  cases  reported  in  literature,  and  in  one 
of  our  collection,  the  usure  also  involves  the  partition  and  the  floor  of  the 
sphenoid  cavities  so  that  a  continuous  bony  defect  is  seen  at  the  base  of  the 
skull.  Otherwise  the  inner  surface  of  the  cavity  of  the  skull  shows  no  con- 
stant changes.  The  lower  surface  of  the  occipital  bone  i<  usually  markedly 
deformed  by  exostoses  at  the  insertion  of  the  muscles.  In  the  skull  in  our 
collection  just  mentioned,  the  external  occipital  protuberance  hangs  like  a 
bent  plug.  The  frontal  bone  is  greatly  thickened,  particularly  at  the  squamous 
base,  so  that  the  superciliary  ridges  stand  out  prominently.  This  thickening, 
however,  i-  not  solid.  It  is  combined  with  a  widening  of  the  air  -pace-  which 
may  Bpread  to  such  an  extent  that  the  frontal  sinus  extend-  throughout  the 
greater  part  of  the  squamous  portion  of  the  frontal  bone.  In  the  bones  of 
the  face  it  is  particularly  the  increase  in  size  of  the  zygomatic  arch  and  the 
lower  jaw  which,  corresponding  to  the  deformities  determined  during  life, 
appear-  in  the  bony  skeleton.  Besides  the  gradual  thickening  and  elongation 
of  the  lower  jaw  anteriorly,  exostoses  at  the  insertions  of  the  muscles  are 
noted.  The  upper  jaw  is  much  less  often  involved  in  this  elongation;  hence 
the  lower  jaw  protrudes.  These  changes  which  are  dearly  noted  only  in  the 
skeleton  -how  that  the  shape  of  the  living  acromegalic's  skull  musl  not  he 
called  recedent  and  prognathous,  as  was  common  before  Sternberg  corrected 
the  new.  In  a  skull  in  my  possession  the  alveolar  process  of  the  incisor  teeth 
i.-  implicated  30  that  by  an  anterior  curvature  of  the  lower  teeth  it  i-  opposed 
to  the  project ing  lower  jaw. 

The  microscopic  examination  of  the  diseased  hone-  -how-  only  that  we 
an-  not  dealing  with  a  specific  process,  but  with  a  deposit  and  absorption  of 
osseous  substance  occurring  in  the  same  manner  a-  in  normal  development. 
In  thi-  connection  it  may  also  be  pointed  out  that  according  to  the  results 
of  Langer,  EQebs,  and  Sternberg,  the  mysterious  influence  of  the  disease  upon 
certain  portions  of  the  osseous  Bystem  may  at  least  he  in  part  understood 
when  we  recognize  that  some  of  The  changes  are  secondary  to  other  and  more 
prominent  alterations.  Thi-  may  be  most  clearly  recognized  upon  the  head. 
"The  marked  development  of  the  apparatus  of  mastication  require«!  a  strong 
foundation  upon  the  head.  This  may  be  furnished  through  thickening  of 
the  -olid  supports,  or  by  dilatation  of  the  hollow  supports,  or  by  an  extension 
of  the  weight  over  ;i  larger  surface.  The  first  requirements  are  fulfilled  by 
the  hypertrophied  zygomatic  arches,  the  second  by  the  widened  air  spaces, 
and  tin1  third  by  the  general  increase  in  the  aize  of  the  bone-  of  the  skull  " 

(  Sterilhep_r  ). 


236  ACROMEGALIA 

This  author  also  attributes  the  changes  in  the  vertebral  column,  in  the 
clavicle,  in  the  muscular  and  ligamentous  insertions  upon  the  occiput  to  one 
predominating  factor,  the  increase  in  weight  of  the  head.  This  view  is  more 
reasonable  than  that  which  explains  the  pathologic  process  as  due  to  a  gen- 
eral irritative  growth  of  bony  tissue.  There  is  another  beautiful  proof  of 
Sternberg's  theory  which,  so  far  as  I  know,  has  not  been  noticed  by  former 
investigators.  The  pneumatic  spaces  in  the  bones  of  the  skull  are  produced 
by  an  absorption  of  the  bony  substance.  The  bone  is  of  the  same  type  as  that 
found  in  the  so-called  "  functional "  bony  structures  which  are  best  recognized 
in  the  spongiosa,  and  which  become  modified  by  the  slightest  pressure  or  the 
slightest  added  weight  of  the  bones  so  as  to  produce  a  structure  suited  to  the 
mechanical  necessities  of  the  situation.  Since  the  functional  structures  in 
acromegalia  (the  frontal  sinuses)  develop  so  enormously,  we  may  look  upon 
this  as  a  proof  that  the  new  formation  of  bone  in  these  cases,  unlike  that  in 
leontiasis  ossea,  or  in'  general  hyperostosis,  is  not  due  to  a  pathologic  osteo- 
plastic activity,  but  is  an  adjustment  to  special  requirements  of  the  bone. 

If,  then,  we  accept  Sternberg's  view,  and  suppose  that  such  a  secondary 
bony  proliferation  accounts  for  the  hypertrophy  of  the  zygomatic  arches,  at 
the  base  of  the  skull,  in  the  vertebral  column,  etc.,  then  the  hyperplasia  of  the 
apparatus  of  mastication,  especially  of  the  lower  jaw,  would  have  to  be 
assumed  as  the  primary  change.  I,  however,  see  no  reason  to  stop  here;  I 
think  we  may  assume  that  the  hyperplasia  of  the  lower  jaw  is  itself  sec- 
ondary, since  this  bone,  too,  shows  throughout  a  uniform  extension,  so  that 
its  deformities  may  be  explained  as  chiefly  the  effect  of  an  increased  strain 
on  the  insertions  of  the  muscles  and  ligaments. 

In  this  case  the  actual  primary  change  would  consist  in  an  enlargement 
of  the  soft  parts,  and  especially  of  the  tongue,  which  may  be  considered  respon- 
sible for  the  position  of  the  jaws  from  the  fact  that  by  its  increased  volume, 
for  which  the  oral  cavity  is  no  longer  adequate,  it  exerts  pressure  upon  the 
jaws.  In  fact  the  macroglossia  is  a  characteristic  feature  of  the  clinical  pic- 
ture, and  to  this  I  should  like  to  ascribe  a  dominant  role  in  producing  the 
change  in  the  face,  including  the  soft  parts,  namely,  the  lips  and  the  nose. 
The  tongue  has  repeatedly  been  examined  microscopically  by  others  as  well  as 
by  myself.  A  prominent  part  in  the  hyperplasia  is  made  up  by  the  mucous 
membrane,  which  is  completely  covered  with  wart-like  proliferations  of  the 
papillae  which  are  also  distributed  in  the  sub-papillary  layers.  Within  the 
muscular  strata  broad,  abnormal,  connective  tissue  strands  appear.  Whether 
the  musculature  itself  is  increased  cannot  be  decided.  From  the  examination 
of  my  preparations  I  do  not,  however,  concur  'in  the  view  sometimes  expressed 
that  degeneration  of  the  muscular  fibers  is  present.  I  was  able,  by  new  stain- 
ing methods,  to  show  the  transverse  sf  Hat  ion  with  such  clearness  that  I  have 
utilized  the  preparations  of  acromegalic  tongues  as  objects  with  which  to 
demonstrate  transverse  striped  muscles.  I  must  assume,  therefore,  that  de- 
generation of  the  tongue  muscles,  like  that  more  frequently  mentioned  in 
the  muscles  of  the  body,  must  be  accounted  for  as  one  of  the  late  marantic 
phenomena  of  the  affection. 

With  Strümpell  I  shall  mention  the  changes  in  the  soft  parts  of  the  ex- 


PATHOLOGICAL  ANATOMY  237 

.tremities,  as  well  as  in  the  face,  which  have  also  been  noted  by  previous  inves- 
tigators, and  shall  regard  them  as  a  feature  more  prominent  than  disease  of 
the  bones.  I  have  already  mentioned  how  slightly  in  some  cases  the  bones 
take  part  in  the  enlargement.  The  principal  mass  of  the  so-called  "  bear's 
paw  "?  is  formed  by  the  soft  parts,  so  that  here  the  conviction  is  almost  forced 
upon  us  that  the  enlargement  of  the  bones,  the  thickening  as  well  as  the 
elongation,  arises  only  secondarily  as  a  support  for  the  increased  mass  of 
the  soft  parts,  and  that  in  the  exostoses  at  the  insertions  of  the  ligaments  and 
muscles  we  may  also  recognize  the  reaction  of  the  enormous  increase  in  weight 
which  is  to  move  the  extremities.  The  hypertrophy  of  the  soft  parts,  as  we 
may  convince  ourselves  both  macroscopic-ally  and  microscopically,  is  due  to 
extremely  tense  connective  tissue  strands  richly  permeated  with  elastic  fibers. 
These  first  thicken  from  the  cutis  itself  downward.  Afterward,  enlarge- 
ment of  the  papillae  and  thickening  of  the  epidermis  become  visible.  The 
connective  tissue  proliferation  is  most  massive  in  the  subcutis,  next  in  the 
deep  fatty  layers  of  the  bands  and  feet.  Each  fat  globule  appears  to  be  sur- 
rounded by  its  own  thick  connective  tissue  capsule,  and  connective  tissue 
forces  its  way  also  between  the  fat-cells  in  thick  layers,  although  we  cannot 
recognize  any  decided  atrophy  of  the  fat-cells.  In  one  of  my  cases  I  found 
the  fat  globules  permeated  in  many  places  by  a  loose  fibrous  connective  tissue 
rich  in  mucin.  Nevertheless,  by  their  outlines  and  by  isolated,  well  preserved 
fat-cells,  the  distribution  of  the  lobules  is  still  easily  recognizable,  also  their 
sharp  Line  of  demarcation  from  the  tense  connective  tissue  of  the  surroundings. 
This  remarkable  condition  of  the  fatty  tissue  accounts  for  the  fact  that,  in 
fresh  sections,  it  exudes  like  a  compressed  filling,  and  gives  the  impression, 
described  by  several  authors,  thai  the  skin  is  too  scant  for  its  content-.  The 
sweat-glands  and  aerve  trunks  of  the  cutis  and  of  the  subcutis  have  their  own 
special  thickened  layers  of  connective  tissue,  and  we  may  note  in  the  cutaneous 
nerve-,  what  Arnold  lir.-t  described,  viz.:  that  connective  tissue  forms  between 
the  individual  fibers.  The  degeneration  particularly  described  by  P.  Marie 
and  Marinescu,  1  could  find  in  only  one  of  the  cases  investigated  by  me,  but 
I  do  not  doubl  that  it  is  frequently  a  natural  consequence  of  the  previously 
described  alterations.  The  same  may  also  be  said  of  the  muscles,  in  which 
also  the  hypertrophy  of  connective  tissue  is  probably  the  primary  factor  and 
degeneration  the  occasional  consequence.  Besides  these  diffuse  changes,  fibro- 
mata molluscs,  papillomata,  and  abnormal  pigmentation  are  also  observed. 
The  sebaceous  glands  and  the  hair  remain  quite  normal,  QOI  was  I  able  to  lind 

any  decided  abnormalities  in  the  vessels. 

PATHOLOGICAL   ANATOMY 

of  the  pathological  findings  in  internal  organs  I  -hall  tir-t  briefly  men- 
tion a  number  of  the  less  constant  ones.  The  internal  organs  may  he  impli- 
cated  in   the  hypertrophy  30  thai    -phinchnoniegalia   ha-  keen   Bpoken  of.      W'e 

cannot,  however,  determine  in  these  findings  in  how    far  the  observers  were 

dealing  with  simple  gigantism,  and    how   far  it    wa-  a   progressive  enlargement 

caused  by  acr -alia.     This  doubl  applies  to  the  large  kidney-  and  livers 


238  ACROMEGALIA 

of  many  acromegalics.  In  other  organs,  as  in  the  heart  and  the  spleen, 
pathologic  enlargements  occur,  yet  they  must  not  be  looked  upon  as  conse- 
quences of  the  acromegalic  process,  but  as  independent  diseases. 

Corresponding  to  the  clinical  symptoms,  the  frequently  determined  hyper- 
plasias or  degenerations  of  the  internal  female  genitalia  and  of  the  testicles 
are  perhaps  in  intimate  relation  to  the  pathologic  process,  while  the  cutaneous 
parts  of  the  external  genitalia  are  frequently  implicated  in  the  acromegalic 
enlargements. 

In  the  pancreas,  connective  tissue  hyperplasia  has  been  described  several 
times.  On  account  of  the  frequent  complication  of  acromegalia  with  dia- 
betes, we  might  easily  interpret  this  as  a  result  of  the  acromegalic  process. 
But  in  the  cases  investigated  by  me,  particularly  in  the  one  combined  with 
diabetes,  the  pancreas  was  perfectly  normal,  while,  in  another  case  in  which 
connective  tissue  increase  was  present,  diabetes  did  not  exist. 

The  central  nervous  system,  i.  e.,  the  base  of  the  brain,  may  be  involved 
directly  and  to  a  marked  extent  by  the  tumor  of  the  hypophysis,  particularly 
the  infundibular  region,  the  pons,  and  the  optic  chiasm.  All  other  findings, 
such  as  column  degeneration  of  the  spinal  cord,  represent  only  accidental 
complications.  In  the  cervical  sympathetic,  Marie  and  Marinescu  found  con- 
nective tissue  increase  and  ganglion  degeneration,  and  this  was  several  times 
confirmed  by  other  observers.  In  my  cases  I  was  unable  to  recognize  decided 
changes  in  this  region. 

The  chief  interest  of  pathological  researches  has  been  concentrated  for  a 
long  time  upon  the  so-called  "  blood-vessel  glands."  Of  these  the  thymus 
gland  first  attracted  attention  for  a  short  time  after  Klebs  had  ascribed  to 
it  a  predominant  role  in  the  disease.  The  enlargement  of  the  thymus  gland 
is,  in  fact,  a  very  frequent  finding.  The  gland  may  extend  into  the  anterior 
mediastinum,  so  as  to  correspond  with  that  of  the  new-born,  though  in  com- 
parison it  is  actually  larger.  The  adrenals  are  large  but  normal.  The  thy- 
reoid gland  may  develop  into  a  massive  goiter,  or  may  be  decidedly  atrophic. 
The  enlargement  may  be  of  any  of  the  types  usually  found  in  goiters,  without 
any  predominant  specific  form  being  recognizable.  The  degenerative  forms  evi- 
dently have  nothing  in  common  with  those  characteristic  of  myxedema.  In  my 
case  the  glomus  carotideum  was  examined,  and  found  to  be  small  and  normal. 

In  the  pathology  of  acromegalia  our  greatest  interest  is  in  the  hypophysis. 
Since  the  first  undoubted  autopsy  findings  of  Verga  in  a  case  of  acromegalia, 
the  characteristic  findings  in  the  skeleton  by  v.  Langer,  and  the  observation 
of  tumors  of  the  mucous  gland  (pituitary  body),  the  autopsies  in  acromegalia 
have  been  more  numerous.  In  accordance  with  the  size  and  character  of  the 
tumor,  the  description  of  the  findings  varies.  There  are  extant  descriptions 
of  the  pituitary  gland  which  show  that  the  authors  did  not  consider  this  to  be 
at  all  enlarged,  and  we  can  only  base  our  assumption  of  an  enlargement  upon 
the  fact  that  masses  were  mentioned  as  present.  In  other  cases  the  enlarge- 
ments are  distinct,  but  only  of  moderate  degree.  Thus,  in  two  cases,  I  have 
found  tumors  about  the  size  of  a  cherry,  one  of  which  eroded  the  groove  of 
the  pituitary  body  and  the  other  the  dorsum  sella?.  The  enlargements  are  of 
every  degree  up  to  the  size  of  a  goose's  egg  or  even  an  apple.     These  either 


PATHOLOGICAL  ANATOMY  239 

develop  downward  and  penetrate  the  entire  sphenoid  bone  to  the  pharynx,  as 
in  a  case  of  Hansemann  and  in  one  of  my  cases,  or  develop  upward  and  com- 
press and  displace  the  organs  at  the  base  of  the  brain,  as  well  as  the  nerves 
and  venous  sinuses  situated  upon  both  sides  of  the  sella  turcica.  This  has 
been  variously  described;  in  one  of  my  cases  the  development  was  upward  and 
also,  to  a  slight  degree,  downward.  The  tumor  invariably  develops  from  the 
anterior  lobe  of  the  gland,  and  in  a  few  eases  has  been  described  a-  simple 
hyperplasia  of  the  gland.  In  other  instances,  adenoma  or  struma  hyperplastica 
of  the  gland  is  directly  mentioned.  Besides  these,  in  still  other  cases,  prolif- 
eration, softening,  cysts  or  connective  tissue  hyperplasia  have  been  found. 
Finally,  in  a  great  number  of  cases  the  tumors  have  been  regarded  as  malig- 
nant. Among  the-r.  isolated  cases  of  gliomata  have  been  mentioned.  Clans 
and  van  dor  Stricht  found  a  lymphadenoma.  The  majority  of  malignant 
tumors  of  the  pituitary  gland  have  been  found  to  be  sarcomata.  Sternberg 
has  laid  particular  stress  upon  the  fact  that  in  the  six  cases  of  malignant 
acromegalia  which  were  known  up  to  the  time  of  the  publication  of  his  mono- 
graph, the  tumors  were  all  sarcomata.  In  the  meantime  Gubler,  in  a  case 
of  malignant  acromegalia  histologically  investigated  by  Hanau,  and  I  myself 
in  at  least  two  cases,  found  tumors  of  the  hypophysis  which  were  similar  to 
the  malignant  variety,  and  which  upon  superficial  examination  might  also 
have  been  looked  upon  as  sarcomatous.  But  we  recognized  the  tumor  cells 
as  originating  from  the  epithelium  of  the  hypophysis,  and  designated  these 
tumors  as  hyperplastic,  and  eventually  as  malignant  adenomata.  Hanau  ex- 
pressed the  suspicion  that  in  the  cases  described  as  sarcomata  the  same  ade- 
nomatous form  of  tumor  h;i-  really  present.  I  was  able  to  demonstrate  in 
my  four  cases  that  the  character  of  the  tumor  was  in  the  main  the  same,  and 
that  its  origin  could  be  found  in  the  glandular  epithelium  of  the  anterior  lobe 
of  the  pituitary  body.  I  wish  to  lay  special  stress  upon  a  fact  (also  noted 
by  Tamburini)  that  in  at  least  three  of  my  cases,  a  large  pari  of  the  tumor 
consisted  of  a  \r\-y  peculiar  form  of  epithelium,  the  "granular  cells,"  which 
correspond  to  the  so-called  chromophilic  cells  of  Flesch.  These  are  the  cells 
which  are  looked  upon  as  the  essentia]  functionating  cell-  of  the  normal  -land. 
I  presume  that  in  every  case  of  hypophysial  tumor  the  hyperplastic  prolifera- 
tion of  the  cells  is  the  K;i-i-  fur  a  Deoplasm,  and  that,  in  the  further  course,  a 

malignanl  degeneration  of  the  tumor  starts  in  these  cells ;  or  a  malignant  pro- 
liferation of  other  tissue  element^  i n ; i \-  replace  this  primary  new  formation 
ami  so  destroy  it. 

When  \\e  consider  the  supposed  Importance  of  the  hypophysial  tumor  in 
the  clinical  picture  of  acromegalia,  we  must  admit  that  it  is  by  no  means 
free  from  objections.  Several  hypotheses  in  marked  contrast  to  each  other 
may  lie  mentioned.  The  most  extreme  (in  one  direction)  assume,  that  the 
tumor  of  the  hypophysis  is  only  a  symptomatic  enlargement  of  the  organ 
which  may  he  markedly  developed,  alightly  developed,  or  entirely  absent,     in 

opposition  to  this  i„  id,,  conception  that  an  abnormal   function  of  the  hvpophy- 

>is  is  tin'  Bole  cause  of  the  disease.      \' more  conservative  view  ascribes  the 

disease  to  a  primary  anomaly  of  the  "  blood-vessel   Lflands,**  among  which   the 

hypophysis  is  to  aome  extent  implicated. 


240  ACROMEGALIA 

The  question  cannot  now  be  determined  with  absolute  certainty  because 
we  must  admit  that  it  is  not  yet  fully  recognized  that  the  hypophysis  is  dis- 
eased in  all  cases  of  acromegalia.  No  less  an  authority  than  R.  Virchow  has 
maintained  from  the  beginning  that  the  changes  in  the  hypophysis  are  a  sec- 
ondary finding  and  were  absent  in  some  of  his  characteristic  cases.  A  case 
from  Virchow's  Institute  has  lately  been  published  by  0.  Israel,  which  appar- 
ently proves  this.  These  extraordinary  differences  in  opinion  can  only  be 
reconciled  by  the  fact  that  the  differential  diagnosis  of  the  disease  is  by  no 
means  so  exact  as  might  appear  from  the  publications  of  P.  Marie  and  Stern- 
berg. It  must  be  borne  in  mind  that  any  of  the  individual  symptoms  of  the 
disease,  the  peculiar  osseous  growth,  the  changes  in  the  soft  parts,  the  macro- 
glossia,  and  even  the  tumor  of  the  hypophysis  may  occur  independently. 
Hence  in  many  cases  a  difference  of  opinion  may  arise  as  to  what  symptom- 
complex  justifies  the  diagnosis  of  acromegalia.  Virchow  lays  great  stress 
upon  the  changes  in  the  bones  of  the  extremities,  and  undoubtedly  has  fur- 
nished incontestable  proof,  which  is  confirmed  by  the  case  of  0.  Israel,  that 
they  also  occur  without  a  tumor  of  the  hypophysis.  This  was  also  recognized 
by  Pierre  Marie  who  diagnosticated  a  similar  disease  of  the  extremities  as 
hypertrophic  osteoarthropathy. 

I  believe,  however,  that  if  we  adhere  to  the  name  acromegalia  for  the 
classical,  clinical  and  anatomical  symptom-complex  of  P.  Marie  alone,  we 
must  admit  that  the  changes  in  the  soft  parts  and  in  the  bones  of  the  face  have 
at  least  as  much  importance  as  those  of  the  bones  of  the  extremities.  In  the 
case  of  Israel  clinical  observation  together  with  the  autopsy  findings  in  the 
bone  reveal,  as  the  celebrated  author  himself  emphasized,  that  other  impor- 
tant symptoms  of  acromegalia  besides  the  tumor  of  the  hypophysis  were  absent. 
It  appears  to  me  most  important  that  there  was  no  record  of  the  acromegalic 
macroglossia  and  the  corresponding  deformity  of  the  lower  jaw.  We  may, 
therefore,  safely  deny  that  this  case  is  acromegalia,  and  must  agree  with  the 
author  that  it  is  inadvisable  to  deduce  from  it  any  far-reaching  conclusions 
as  to  the  nature  of  acromegalia. 

The  fact  is  much  more  important  that  in  literature  quite  a  number  of  cases 
are  mentioned  in  which  true  adenomata  of  the  hypophysis  were  found  with- 
out acromegalia.  I  still  entertain  the  hope  that  by  careful  investigation  with 
the  most  approved  methods  we  may  find  these  tumors  to  deviate  from  the  type 
of  those  occurring  in  acromegalia.  In  a  case  recently  examined  by  me,  the 
question  arises  whether  the  age  of  the  patient,  sixty  years,  might  not  explain 
the  absence  of  corresponding  general  symptoms.  Opposed  to  the  view  that 
the  tumor  of  the  hypophysis  is  a  symptom  and  not  the  cause  of  acromegalia 
is  the  fact  that  the  common  type  of  Irypophysial  tumors  differs  from  the  normal 
structure  of  the  gland  (as  was  especially  apparent  in  all  of  my  four  cases  which 
were  minutely  investigated)  as  well  as  from  the  other  acromegalic  hyper- 
plasias, which  in  the  main  are  composed  of  connective  tissue. 

The  opinion  that  disease  of  the  hypophysis  produces  the  symptoms  of 
acromegalia  only  by  co-operation  with  the  other  blood-vessel  glands  is  not  in 
accordance  with  the  fact  that  no  other  blood-vessel  gland  is  so  constantly 
involved  in  the  disease  as  the  pituitary  body.     Indeed  this  is  not  even  approxi- 


PATHOLOGICAL  ANATOMY  241 

mately  the  case.  The  symptoms  which  have  been  recognized  as  consequences 
of  diseases  of  the  other  blood-vessel  glands  are  generally  absent  in  the  clinical 
picture  of  acromegalia;  or,  if  they  do  occur,  they  represent  distinct  compli- 
cations, and  the  characteristic  changes  of  acromegalia  are  not  produced  by 
disease  of  any  of  them.  Finally,  the  especial,  peculiar,  histological  structure 
of  the  hypophysial  disease  favors  the  opinion  that  this  plays  a  role  entirely 
different  from  that  of  the  other  blood-vessel  glands. 

In  so  far  as  we  can  arrive  at  logical  conclusions  by  exclusion  and  without 
experiment,  we  may  maintain  the  view  which  was  first  expressed  by  Pierre 
Marie  that  disease  of  the  hypophysis  is  the  etiologic  factor  in  acromegalia. 

We  will  now  consider  in  what  manner  the  hypophysis  causes  the  disease. 
The  original  view  of  Pierre  Marie  that  the  changes  are  due  to  an  absence 
of  function  of  the  degenerated  hypophysis — as  in  myxedema  by  an  absence  of 
function  of  the  thyreoid — is  not  substantiated  by  our  more  exact  knowledge  of 
the  character  of  the  glandular  proliferation.  Somewhat  more  reasonable  and 
better  founded  are  the  hypotheses  of  Hansemann  and  Uthoff,  who  hold  that 
the  relation  between  the  enlargement  of  the  hypophysis  and  the  affected  parts 
is  an  altruistic  hyperplasia.  In  whatever  way  the  progressive  development  of 
the  hypophysis  is  produced,  in  that  way  the  progressive  development  of  other 
parts  (extremities,  bones  of  the  face  and  internal  organs)  is  also  brought 
about.  According  to  Hansemann,  altruistic  hyperplasia  may  occur  with  organs 
that  have  an  embryologic  connection. as  between  the  anterior  lobe  of  the  hypoph- 
ysis and  the  tongue,  but  we  can  hardly  say  that  there  is  any  Buch  relation 
between  the  gland  and  the  extremities.  This  view  becomes  even  less  tenable 
when  it  is  clearly  demonstrated  that  neither  the  changes  of  the  hypophysis 
nor  those  of  the  extremity  represent  simple  progessive  hyperplasia,  and  that 
in  both  we  are  dealing  with  new  tumor-like  formations  of  entirely  atypical 
nature. 

In  my  previously  published  articles,  I  have  accepted  the  view  of  Tamburini, 
as  do  also.  Hanau  and  Woods  Hutchinson,  that  the  pathologic  development  of 
the  hypophysis  is  due  to  a  hyperactivity  and  over-production  of  the  secre- 
tion which  is  to  be  utilized  internally.  Tamburini,  at  any  rate,  attributes 
the  phenomena  of  .growth  to  these  causes,  while  the  cachexia  observed  in  the 
later  stages  of  the  disease  is  regarded  as  a  consequence  of  the  adenomatous 
and  cystic  degeneration  of  the  gland.  For  Beveral  reasons  this  theory  must 
now  be  somewhat  modified.  First,  in  its  original  form,  the  division  of  the 
disease  into  two  phases  is  impossible.  On  the  contrary,  in  the  purest  type 
of  acromegalia,  Sternberg's  malignant  form,  the  development  of  the  tumor 
of  the  hypophysis  is  unquestionably  combined  with  symptoms  of  peripheral 
hyperplasia  and  the  injurious  effects  of  this  upon  the  entire  organism.  Tam- 
burini's  theory  is  also  difficult  of  acceptance  because  it-  adherents,  as  well 
as  its  opponents,  have  hem  forced  to  the  conclusion  that  if  his  dews  are  cor- 
rect, the  secretion  of  the  hypophysis  must  also  influence  the  normal  growth 
of  the  body  j  \\'ood<  Hut  chin-on  has  gone  so  far  as  to  declare  that  the  hypophy- 

si-  is  the  center  for  body  growth. 

These  difficulties  lessen  when  the  processes  of  peripheral  growth  are  recog- 
nized as  constant  but  Less  important  consequences  of  acromegalia  (which  is 

17 


242  ACROMEGALIA 

clear  to  me),  and  the  true  nature  of  the  disease  is  conceived  as  a  tumor-like 
formation  in  the  connective  tissue  which,  as  Erb  and  Ponfick  have  already 
pointed  out.  resembles  that  of  elephantiasis  and  also  myxedema.  It  might 
be  more  easy  to  ascribe  the  symptoms  of  the  disease  to  the  action  of  a  specific 
toxic  secretion  which,  under  normal  circumstances,  possesses  an  unknown 
function,  and  which  is  present  in  the  circulation  in  such  slight  amounts  that 
no  deleterious  effect  is  produced.  I  refer  to  the  zymogen-like  granules  secreted 
in  the  chromophilic  cells  which,  in  at  least  three  of  my  cases,  I  found  enor- 
mously increased,  while  in  the  normal  gland  their  action  appeared  of  less 
importance.  I  believe  it  may  be  strictly  maintained  that  if  there  is  a  lessen- 
ing of  the  normal  supply  of  the  bodies  to  the  circulation  they  may  affect  the 
activity  of  digestion  as  profoundly  as  the  blood  plasma  as  shown  by  recent 
investigations.  Hence  an  over-production  of  them  may  cause  severe  damage 
to  the  tissues  of  the  body. 

TREATMENT 

In  conclusion  I  shall  refer  briefly  to  the  therapy  of  the  affection.  I  have 
only  negative  points  to  report,  since,  up  to  the  present  time,  it  has  been  abso- 
lutely without  effect.  Yet  a  knowledge  of  the  pathology  of  the  disease  may 
prevent  error  in  the  choice  of  therapeutic  measures.  The  uncritical  way  in 
which  organotherapeutic  "  curative "  results  have  been  published  led,  as  a 
matter  of  course,  to  the  production  of  hypophysis  tablets  and  their  admin- 
istration to  acromegalics  as  soon  as  it  became  known  that  in  acromegalia  the 
hypophysis  appeared  to  be  affected.  Fortunately,  it  has  been  demonstrated 
both  by  the  use  of  these  and  by  animal  experiment  that  the  administration  of 
the  pituitary  gland  by  mouth  is  quite  harmless;  we  may  assume  that  its 
active  constituents  are  rendered  inert  by  the  digestive  fluids.  Otherwise,  we 
would  realize  the  unpleasant  truth  that  this  therapy  must  aggravate  the  dis- 
ease by  increasing  the  materia  peccans.  Until  a  hypophysis  antitoxin  is  pro- 
duced, the  only  rational  treatment,  based  on  the  pathology  of  the  disease, 
must  be  the  extirpation  of  the  hypophysial  tumor.  We  cannot  understand 
why  the  hand  of  the  fearless  surgeon  who  has  dared  to  attack  the  neighboring 
Gasserian  ganglion  should  halt  at  this  operation. 


CHRONIC    ARTICULAR     RHEUMATISM 

By    \V.    HIS,    Basel 

In  attempting  to  describe  a  disease  so  familiar  ami  commonplace  as  chronic 
articular  rheumatism  (this  appears  to  be  the  prevalent  opinion  in  regard  to 
it),  it  is  almost  necessary  to  begin  with  a  captatio  benevolenticB.  A  few  years 
ago,  when  I  began  to  study  this  disease  somewhal  in  detail,  I  learned  that  it 
had  long  attracted  the  attention  of  many  scientists.  The  Lasl  of  the  greater 
compilation-,  thai  by  Pribram,  although  by  no  moans  exhaustive,  contains 
notes  of  over  500  investigations  which  refer  to  chronic  articular  rheumatism, 
and  among  the  authors  are  fouml  the  most  prominent  name-  in  medical  sci- 
ence, of  uiiom  I  -ball  mention  Charcot,  Bouchard.  Lancereaux,  Pierre  Marie 
in  France,  the  Garrods,  father  and  son,  in  England,  Richard  Volkmann, 
Senator.  Bäumler,  and  Albin  Hoffmann  in  Germany. 

The  disease  is  by  no  mean-  a  new  one:  it  was  familiar  to  the  ancients 
who  confounded  it  with  gout  and  designated  it  by  the  collective  term  arthritis. 
It  was  not  until  the  year  L800  thai  Landre-Beauvais  expressly  pointed  out 
thai  the  disease  was  a  distinct  entity.  Alfred  Garrod  in  his  celebrated  book 
od  goul  proved  thai  the  deposil  of  urate  salts  which  is  the  materia  peccans 
in  the  joints  affected  by  goul  never  occur-  in  chronic  articular  rheumatism. 
Nevertheless,  there  are  -nil  some  authors  who.  even  in  recent  years,  have 
endeavored  to  merge  the  two  diseases,  believing  them  to  be  one.  This  attempt 
i-  due  to  the  fact  thai  certain  phenomena  in  the  joints,  and  many  of  the 
accompanying  and  subsequenl  symptoms  in  both  diseases,  may  be  the  Bamej 
we  shall  refer  later  to  this  point  more  in  detail. 

The  manifestations  of  chronic  articular  rheumatism  are  very  various,  and 
if  the  descriptions  of  differenl  authors  are  compared  with  one  another,  it  i- 
often  difficull  to  believe  thai  they  are  portraying  the  same  disease.  Whal 
one  experienced  observer  describes  as  a  frequent  finding,  another,  no  less 
experienced,  has  scarcely  ever  seen.  Similar  to  this  is  the  variety  of  opinions 
in  regard  to  the  etiologj  ;  greater  diversity  of  views  can  scarcely  be  conceived. 
According  to  some  authors,  for  instance,  M.  Schiiller  and  Bannatyne,  chronic 
rheumatism  is  an  infectious  disease  in  which  there  can  be  invariably  demon- 
strated certain  microorganisms j  toothers  (Bouchard,  Lancereaux)  the  disease 
i-  the  expression  of  a  constitutional  anomaly  which  is  markedly  hereditary, 
running  in  families,  and  Bhowing  itself  by  numerous  other  symptoms.  Other 
writer-  believe  tbat  the  affection  is  in  the  main  a  local  process  confined  to  the 
joints  and  periarticular  tissues.  Finally,  there  are  Borne  who  consider  it  a 
disease  of  the  cenl  raJ  nervous  -\  stem. 


244  CHRONIC  ARTICULAR  RHEUMATISM 

Just  as  diverse  is  the  nomenclature.  Almost  every  author  has  attempted 
to  arrange  the  varying  pathological  pictures  in  distinct  groups  (all  mentioned 
by  Pribram),  and  of  the  names  that  have  been  chosen  some  refer  to  the  clinical 
course  (for  instance,  Charcot's  rheumatism/1  articulaire  chronique  progressif). 
some  to  the  shapes  assumed  by  the  joint  {arthritis  deformans  of  Virchow  and 
E.  Volkmann,  rheumatisme  noueux  of  Trousseau),  some  to  the  anatomical 
findings  (M.  Schiiller's  polyarthritis  villosa)  and  some  to  their  authors'  etiolo- 
gic  views,  for  example,  rheumatisme  goutteux,  diathesique  (Pierre  Marie)  and 
infectieux  (Teissier  and  Roque). 

This  confusion  is  increased  by  the  fact  that  the  same  title  is  applied  to 
quite  opposite  pathological  conditions.  Thus,  the  rheumatisme  deformant  of 
the  French,  with  effusion,  proliferation  of  the  capsule,  and  spindle-shaped 
swelling  of  the  joint,  is  identical  with  what  the  German  surgeons  and  clin- 
icians (following  R.  Volkmann)  call  chronic  rheumatism  in  contrast  with 
arthritis  deformans,  which  is  characterized  by  atrophy  of  the  capsule  and 
proliferation  of  the  bone,  in  many  joints  or  in  one  alone  (for  example,  the 
malum  senile  coxa?). 

This  confusion  can  only  be  cleared  up  by  describing  briefly  all  the  principal 
types  of  joint  disease. 

1.  When  a  young  person,  after  brief  prodromal  symptoms  or  a  tonsilitis 
with  fever,  is  attacked  with  painful  swelling  of  the  joints,  the  inflammation 
spreading  from  one  joint  to  another,  affecting  large  and  small  joints  alike, 
and  without  predilection  for  any — when  the  endocardium,  the  myocardium, 
the  pericardium,  the  pleurae,  perhaps  even  the  meninges  are .  involved — we 
recognize  in  this  picture  an  infectious  disease,  acute  articular  rheumatism, 
and  we  know  that,  as  a  rule,  it  runs  its  course  without  leaving  permanent 
changes  in  the  joints.  Exceptionally,  however,  swelling  of  one  or  more  joints 
and  moderate  pain  and  stiffness  remain.  After  weeks  or  months  the  joint 
function  is  more  or  less  completely  restored  or  the  diseased  condition  becomes 
permanent.  This  is  chronic  arthritis,  resulting  from  an  attack  of  typical 
acute  articular  rheumatism. 

Now  as  the  primary  forms  of  chronic  arthritis  may  begin  with  acute 
febrile  attacks,  their  differentiation  is  often  difficult.  Davaine  closely  studied 
the  disease,  and  laid  especial  stress  upon  possible  prodromes,  splenic  tumor, 
visceral  complications,  the  ease  with  which  the  effusion  in  the  joint  may  be 
displaced,  the  absence  of  trophic  disturbances  (atrophy  of  the  muscles),  and  the 
absence  of  family  predisposition  to  acute  articular  rheumatism.  Unquestion- 
ably Davaine  has  arranged  this  in  too  schematic  a  manner,  and,  therefore, 
in  any  individual  case  we  may  waver  for  a  time  in  our  decision;  the  occur- 
rence of  secondary  chronic  rheumatism  is,  however,  recognized  by  all  later 
authors. 

2.  The  second  form  is  prone  to  attack  persons  between  thirty  and  forty 
years  of  age.  The  disease  is  ushered  in  with  fever  and  pains  in  the  joints, 
which  are  swollen  but  not  to  the  same  extent  as  in  acute  rheumatism.  They 
have  an  elastic,  tense  feeling,  but  fluctuation  is  obtained  with  difficulty;  the 
skin  is  slightly  reddened,  and  is  edematous  above  and  below  the  joint  so  that 
the  affected  joint  shows  a  spindle-shaped  swelling.     Gradually  new  joints  are 


CHRONIC  ARTICULAR  RHEUMATISM  245 

attacked  or  those  affected  improve,  but  a  number  of  those  first  attacked  always 
remain  permanently  diseased. 

The  joints  exhibit  conspicuous  regularity  in  the  order  of  their  involve- 
ment. First,  the  smaller  joints  of  the  body  are  attacked;  the  phalangeal  and 
interphalangeal  joints  of  the  fingers  with  the  exception  of  the  thumb,  the 
corresponding  joints  of  the  toes,  then  those  of  the  hands,  of  the  elbows  and 
knees;  the  shoulder  and  hip  are  almost  always  exempt.  The  disease,  how- 
ever, shows  a  preference  for  certain  joints  which  are  usually  spared  by  acute 
polyarthritis,  Buch  as  the  jaw.  the  sternoclavicular  joint  and  the  sternocostal 
joints.1  Secondly  the  affection  is  conspicuously  symmetrical :  Almost  always 
both  hands,  both  feet,  both  knees  are  attacked ;  only  the  joints  mentioned 
above  are.  as  a  rule,  attacked  unilaterally.  The  further  course  of  the  disease 
varies.  Either  the  joints  return  more  or  Less  to  the  normal,  to  be  similarly 
attacked  after  months  or  years  (often  acutely  and  with  fever)  or  the  affection 
is  "chronic  from  the  onset,"  and  in  time  changes  occur  in  the  joints  which 
prefigure  the  third  form  now  about  to  be  described. 

3.  The  third  form  generally  attack-  elderly  persons,  particularly  women 
during  the  menopause;  the  disease  begins  with  indistinct  nervous  sympto 
drawing  or  tearing  pains,  furry  sensations  or  formication,  sensations  of  cold. 
etc.,  in  the  hands  and  feet.  The  patients  notice  that  the  motility  of  the 
fingers  gradually  decreases.  Fine  movements  such  as  sewing,  knitting,  writ- 
ing, become  difficult,  particularly  in  the  morning  and  during  cold  weather. 
Careful  observers  note  that  the  end-  of  the  joints  and  the  basic  and  inter- 
phalangeal joints  are  slightly  thickened;  they  feel  hard  and  are  not  very 
tender  on  pressure.  The  fingers  gradually  defied  toward  the  ulnar  side,  and 
this  is  firsl  noticeable  in  the  proximal  joint  with  the  extended  interphalangeal 
joints;  finally  complete  subluxation  results  in  the  basic  joint,  though  in  this, 
as  well  as  the  other  changes,  the  thumb  is  rarely  implicated.  The  inter- 
osseous -pace-  show  deep  grooves;  the  hall  of  the  thumb  and  little  finger  are 
atrophied.  The  same  changes  take  place  in  the  toes.  Muscular  contractures 
appear  early  and  cause  abnormal  positions  of  the  extremities.  Charcot,  with 
his  artistic  mind,  attempted  to  arrange  these  positions  according  to  a  Bystem: 
A  flexion  and  an  extension  type  (more  correctly  a  hyper-extension  type)  each 
type  with  several  sub-varieties.  If.  with  Vidal,  we  accept  also  an  extension 
type  (straight  line)  every  imaginable  form  results,  and  if  we  reflecl  that  the 
fingers  of  the  same  hand  may  present   various  types  side  by  side,  the  value 

of  this  schematic  division  will  not  appeal-  great.  Besides  the  muscular  con- 
tracture, changes  in  the  joints  add  to  the  immobility;  the  capsule  shrinks  to 
fibrinous  strands,  the  surfaces  of  the  joints  coalesce  by  connective  tissue  Liga- 
ments, exostoses  and  ecchondro8es  appeal-:  The  final  result  in  well  marked 
cases  is  complete  immobility  of  the  joints  in  abnormal  positions;  the  unfor- 
tunates are  condemned  to  permanenl  invalidism,  and  till  a  large  part  of  our 
almshouses  and  home-  for  incurables. 

This  form  differs  from  the  two  firs!  mentioned  by  its  gradual  and  afebrile 


i  These,  however,  although  rarely,  are  Bometimee  attacked  in  acute  polyarthritis j 
indeed,  the  jaw  may  be  the  only  joint  attacked   I  Eamrn,  Manage» 


246  CHRONIC  ARTICULAR  RHEUMATISM 

onset,  its  slow  course,  the  absence  of  effusion  into  the  joints,  cutaneous  edema 
and  capsular  swelling.  It  resembles  them  in  a  preference  for  the  small  joints 
and  in  the  conspicuous  symmetry;  moreover,  every  possible  transitional  form 
occurs,  so  that  they  can  only  arbitrarily  be  differentiated.  More  correctly, 
perhaps,  we  may  call  them  different  developments  of  the  same  disease.  There- 
fore I  have  not  yet  accepted  the  division  which  is  often  made  (lately  by 
Curschmann)  into  chronic  articular  rheumatism  and  arthritis  deformans.  I 
agree  with  Charcot,  who  designates  the  two  as  the  exudative  and  the  dry 
form  of  'primary  chronic  progressive  polyarthritis. 

4.  The  fourth  form  is  characterized  by  appearing  in  elderly  persons  and 
in  the  aged,  by  a  markedly  chronic  course,  by  invariable  limitation  to  one 
or  more  large  joints,  and  frequently,  although  not  always,  by  its  connection 
with  trauma.  This  is  the  arthritis  deformans  of  R.  Volkmann,  the  rheuma- 
tisme  chronique  partiel  of  Charcot,  the  best  known  type  of  which  is  the  malum 
senile  coxa?.  But  this  affection  is  not  infrequently  noted  in  the  fourth  and 
fifth  decades  of  life,  most  often,  perhaps,  in  the  shoulder  after  a  fall  or 
contusion. 

Effusion  is  almost  always  absent.  When  the  patient  is  at  rest  the  pains 
are  moderate  or  cease  entirely;  movement  is  limited  to  a  great  extent,  muscle 
contractions  or,  at  least,  constrained  positions,  generally  occur  and  atrophy 
is  frequent  (in  the  shoulder,  mostly  of  the  deltoid  and  triceps).  Upon  move- 
ment, friction  and  cracking  are  heard  and  felt  in  the  ends  of  the  joints.  After 
the  disease  has  lasted  a  long  time  deformities  due  to  exostoses  and  ecchon- 
droses  invariably  appear.     These  will  be  described  below. 

5.  The  fifth  form  includes  the  chronic,  deforming  and  ankylosing  dis- 
eases of  the  vertebral  column  (Pribram).  Julius  Braun,  in  1875,  was  the 
first  to  collect  a  large  number  of  cases.  Strümpell  described  the  implication 
of  the  hip-joint  in  arthritis  of  the  vertebral  column.  Pierre  Marie  in  1898 
worked  out  the  symptomatology  of  "  Spondylose  rhizonieUque  "  which  appears 
in  men  immediately  after  the"  completion  of  their  growth,  and  consists  in  com- 
plete adhesion  of  all  vertebras,  scoliosis  and  kyphosis  of  the  shoulder-  and  hip- 
joints,  but  with  intact  extremities.  Another  form  was  described  by  Bechterew 
in  1892  :  Limited  movement  in  the  vertebral  column  with  anterior  curvature, 
particularly  of  the  upper  parts;  associated  with  this  pareses  of  the  muscula- 
ture of  the  neck,  trunk  and  extremities,  and  atrophy  of  the  muscles  of  the 
back  and  scapula.  Common  to  both  of  these  forms  are  nervous  disturbances 
— anesthesia  and  paresthesia,  neuralgia,  paralyses  and  muscular  atrophies  in 
varying  form  and  extent.  The  Strümpell-Marie  form  distributes  itself  from 
below  upward;  Bechterew' s  variety  from  the  shoulder  to  the  hip. 

In  the  meantime,  in  a  large  number  of  observations,  particularly  those 
compiled  by  W.  Anschiitz,  it  was  noted  that  a  sharp  differentiation  of  these 
forms  is  impracticable,  that,  on  the  contrary,  numerous  transitional  stages 
are  observed.  Some  of  these  begin  at  the  upper  or  lower  end  of  the  vertebral 
column,  with  or  without  involvement  of  the  joints  of  the  trunk,  or,  finally, 
in  combination  with  chronic  arthritis  of  the  extremities  in  one  or  another 
order.  Joh.  Müller  described  a  case  with  extreme  stiffness  of  the  articulations 
of  the  ribs,  respiration  being  maintained  entirely  by  the  diaphragm  and  the 


CHRONIC  ARTICULAR  RHEUMATISM 


247 


abdominal  muscles;  Clarke  described  a  disease  confined  to  the  costovertebral 
joints  of  the  twelfth  pair  of  ribs.  Anatomically  the  process  produces  changes 
in  the  ligaments  of  the  intervertebral  sheaths  and  of  the  vertebral  joints  in 
varying  combinations  (Schlesinger)  ;  the  nervous  disturbances  are  partly  due 
to  compression  of  the  nerve  roots,  partly  to  chronic  meningitis  (Bechterew). 
Etiological^  we  must  consider  primary  and  secondary  chronic  arthritis,  arthri- 
tis deformans,  gonorrhea,  syphilis  and  other  infections.  Whether  the  affections 
confined  to  the  ligamentous  apparatus  and  intervertebral  sheaths  are  to  be 
classed  as  chronic  arthritis  may  be  questionable.  Bäumler  calls  attention  to 
the  fact  that  stiffness  of  the  hip-joints  and  lower  vertebral  articulations  in 
consequence  of  the  patient's  increased  weight  may  lead  to  disease  of  the  upper 
vertebra1.  R.  Bennecke  lays  stress  upon  the  action  of  frequent,  though  insig- 
nificant, trauma  upon  the  vertebral  sheaths  and  bony  structures.  In  conclu- 
sion, similar  clinical   pictures   are  presented    by  contracture  of   the  lumbar 


Fio.  4.     Röntgen    P u    Showing    Heberden's    Nodes    upon    ran    Km  \-    wn    Littlh 

Finger,  wnii  Exostoses  01   mm   Second  lnd   Chird  Phalanges. 


248  CHRONIC  ARTICULAR   RHEUMATISM 

muscles  and  those  of  the  back.  Beer,  Zenner,  and  lately  Cassirer  and  Senator 
have  described  such  "  myogenous  "  vertebral  stiffness,  some  of  which  may  be 
due  to  hysteria  and  some  to  acute  fibrous  myositis. 

These  conditions  indicate  that  chronic  rigidity  of  the  vertebra  may  be 
due  to  very  different  causes,  but  we  may  be  certain  that  those  forms  which 
occur  in  connection  with  acute  or  chronic  articular  rheumatism  or  with  disease 
of  the  joints  of  the  extremities  should  be  classed  as  chronic  arthritis. 

6.  As  the  sixth  and  last  type,  I  must  mention  those  almost  painless  or 
only  temporarily  painful  nodes  which  occur  in  the  terminal  joint  of  the  three- 
jointed  fingers,  appearing  upon  their  posterior  surface,  giving  them  an  oval 
shape,  hard  to  the  touch,  and  gradually,  from  rigidity  of  the  joint,  fixing  the 
fingers  in  a  position  of  flexion  or  abduction.  They  are  often  looked  upon  as 
the  signs  of  uric  acid  gout;  E.  Pfeiffer  believes  them  to  be  a  certain  guide 
in  diagnosis  even  in  the  absence  of  other  gouty  symptoms. 

Heberden,  who  discovered  them,  did  not  attribute  them  exclusively  to 
gout,  and  I  coincide  in  the  opinion  of  the  majority  of  later  authors  who  find 
these  Heberden's  nodes  occasionally  in  gout,  occasionally  in  chronic  arthritis, 
but  most  often  as  the  only  arthritic  symptom  in  otherwise  healthy  individuals. 
The  Röntgen  picture  shows  them  to  be  exostoses,  and  they  form  a  connecting 
link  between  chronic  rheumatism  and  arthritis  deformans;  with  the  former 
they  have  in  common  symmetry  and  multiplicity,  with  the  latter,  the  bony, 
marginal  proliferations,  and  the  usually  painful  and  chronic  course.  It  is 
well  to  follow  Charcot  and  to  separate  them  as  special  forms  of  disease. 

This  finishes  the  description  of  the  most  common  types;  but  it  must  be 
added  that  in  individual  cases  transitional  stages  occur  which  tend  to  merge 
the  types  into  each  other.  For  this  reason  clinical  findings  do  not  permit  a 
fine  differentiation,  and  an  attempt  has  been  made  to  found  a  classification 
upon  the  anatomical  changes. 

PATHOLOGY 

The  anatomical  changes  extend  to  all  parts  of  the  joint,  cartilage,  bone 
and  capsule,  and  frequently  also  to  the  adjoining  muscles,  tendons  and  tendon 
sheaths.  In  the  earlier  stages  these  changes  are  relatively  but  little  known; 
they  are  found  as  accidental  lesions,  and  often  run  their  course  during  the 
life  of  the  patient  without  symptoms.  Thus,  the  patient  from  whom  illustra- 
tion 5  was  taken  was  a  chorus  girl  and  dancer  until  a  few  weeks  before  her 
death.  Moderate  changes  are  noted  by  surgeons,  who  look  upon  chronic 
rheumatism  as  a  border-land  which  should  be  gradually  brought  under  their 
dominion.  The  later  changes  are  well  known  anatomically,  but  they  illumi- 
nate the  problem  of  their  origin  as  poorly  as  ulcerative  phthisis  explains  the 
onset  of  pulmonary  tuberculosis. 

Even  to-day  it  is  not  quite  clear  whether  the  affection  begins  in  the  car- 
tilage of  the  joint  or  in  the  synovial  membrane.  Sometimes  the  one,  some- 
times the  other,  appears  to  be  the  case;  nevertheless  both  are  early  attacked. 
In  the  cartilage  the  basic  substance  appears  completely  detached,  the  cartilage 
cells  proliferated,  and  sometimes  discharged  from  their  capsules  into  the 
joint  fluid. 


PATHOLOGY 


249 


In  some  forms  the  amount  of  synovial  fluid  is  increased,  occasionally 
turbid  but — and  this  is  characteristic  of  chronic  arthritis — never  purulent. 
The  villi  of  the   synovial  membrane  are  hyperemic    (violet  red),   showing 


Fig.  f>. — Metatarsophalangeal  Articulation  of  a  Chori^s  Girl,  Aged  1  orty-Five,  with 
Beginning  Chronic  Arthritis  without  Symptoms;  Death  from  Contra«  ran  Kidni  v. 
Fibrillation  of  the  cartilaginous  basic  substance,  proliferation  of  the  cartilage  cells,  the 
capsules  of  which  partially  open  into  the  joinl  cavity.     The  capsule  of  the  join  1  is  intact. 

marked  proliferation;  occasionally  fatty  degeneration  is  noted  (lipoma  arbo- 
rescens),  ami  in  well  developed  cases  preseni  the  appearance  of  sheep's  wool; 
the  capsule  and  its  surroundings  show  edematous  infiltration.  The  bone 
appears  unchanged  in  the  early  Btages  of  the  disease. 

In  later  Btages  the  smooth  surfaces  are  denuded  of  cartilage,  the  bone  is 
bare,  and.  if  joint  movements  have  -till  been  performed,  sIihw>  grooves,  re- 
sembling tin'  crevasses  of  a  -lacier,  often  the  bared  surface  is  dense  and 
ivory-like,  or  it  is  covered  by  connective  tissue  which  extend-  from  the  borders 
of  the  synovial  membrane,  from  transformed  cartilage  cell-,  or  even  from 
the  surfaces  hare  of  cartilage.  This  connective  tissue  covers  the  joint  surface 
(Kachel),  and  frequently  adheres  to  the  opposing  joinl  <w,\~  (fibrous  anky- 
losis). These  connective  tissue  stria?  may  calcify  and  finally  ossify  (bony 
ankylosis).  Upon  the  border  of  the  cartilage,  wherever  it  is  covered  by 
synovial  membrane,  ecchondroses  develop  which  are  transformed  into  osteoids 
and  finally  into  bony  tissue.  By  these  exostotic  marginal  proliferations,  the 
joint  end  attains  a  mushroom  form  and  resembles  the  crown  of  the  antler 
of  a  deer. 


250  CHRONIC  ARTICULAR  RHEUMATISM 

The  bony  substance  becomes  rarefied  and  fragile,  the  capsule,  which  was 
at  first  flaccid,  proliferated,  and  infiltrated  with  serum,  is  transformed  into 
fibrous  tissue  which  cicatrizes  around  the  ends  of  the  joint  and  limits  motion. 
In  the  proliferated  villi,  islands  of  cartilage  or  bony  tissue  form,  and  these 
may  be  thrown  off  as  free  joint  bodies.  The  final  stage  is  complete  osseous  or 
fibrous  ankylosis  of  the  joint  which  is  fixed  in  more  or  less  unnatural  position 
and  greatly  deformed. 

All  these  processes  are  common  to  the  various  forms  of  chronic  arthritis; 
at  one  time  one,  at  another  time  another,  becomes  prominent.  Thus,  in  the 
exudative  form  of  progressive  chronic  polyarthritis,  proliferation  and  edema- 
tous infiltration  of  the  synovial  membrane  and  its  surroundings  dominate 
the  situation,  hence  the  spindle-shaped  form  of  the  joints.  The  cartilage 
often  appears  to  be  secondarily  implicated. 

In  polyarthritis  "  sicca  "  which  has  a  chronic  beginning,  the  proliferation 
of  the  joint  is  not  as  marked  as  the  fibrous  transformation  of  the  cartilage. 
The  outlines  of  the  joint  ends  as  a  consequence  of  this  become  prominent, 
and  exostoses,  if  present,  may  be  felt  through  the  tense  skin  as  hard,  prom- 
inent nodules  which  may  sometimes  be  seen.  This  form  also  shows  a  tendency 
to  fibrous  ankylosis.  In  senile  deforming  monoarthritis  these  osseous  border 
proliferations  with  disappearance  of  cartilage  play  the  main  role  in  the  limita- 
tion of  movement ;  the  capsule  forms  no  essential  part  of  the  clinical  picture. 
Finally,  Heberden's  nodes  are  exostoses  which  at  first  slightly  limit  motion. 

If  the  anatomical  descriptions  of  later  authors  are  compared  (particularly 
Schuchardt  and  Weichselbaum)  we  are  forced  to  agree  with  Charcot  who 
declines  sharply  to  separate  the  forms  according  to  the  anatomical  findings. 
He  regards  them  as  in  some  sense  branches  of  the  same  trunk. 

CLINICAL   SYMPTOMS 

The  clinical  picture  would  be  incomplete  if  only  the  joint  lesions  were 
considered.  Very  frequently  there  is  early  impairment  of  the  general  health. 
The  cases  occurring  in  young  persons  with  fever  are  particularly  apt  to  show 
from  the  onset  emaciation  and  conspicuous  cachexia.  This  can  hardly  be 
attributed  to  the  fever.  Occasionally  the  fever  lasts  for  weeks  and  reaches 
102°  F.  and  higher,  but  there  is  no  proportion  between  the  height  or  duration 
of  the  fever  and  the  emaciation.  Indeed  even  after  the  temperature  falls  the 
patients  remain  weak.  The  inactivity  of  the  patient,  the  want  of  fresh  air, 
and  the  constant  pain  have  been  urged  in  explanation.  But  if  we  bear  in  mind 
that  patients  with  disease  of  the  spinal  cord  become  abnormally  fat  despite 
the  fact  of  constant  pain  and  immobility,  we  cannot  concur  in  this  view, 
but  must  look  upon  these  forms  of  arthritis  as  conspicuous  instances  of 
wasting  disease.  Amyloid  degeneration  (Roese)  which  frequently  appears 
confirms  this.  It  is  true  other  cases  of  arthritis  belong  to  the  fat  plethoric 
type  and  here  also  transitional  cases  are  recorded.  Frequently,  particularly 
in  the  young,  there  is  moderate  anemia  and  oligocythemia. 

Most  of  the  muscles  of  the  body  take  part  in  the  emaciation ;  in  some  cases 
the  entire  musculature  suffers  but  almost  invariably  the  muscles  in  the  neigh- 


CLINICAL  SYMPTOMS  251 

borhood  of  the  joints  are  involved,  and  among  these  the  extensors  are  most 
seriously  affected.  If  rheumatism  attacks  the  hand  the  interossei  atrophy  very 
early,  often  before  the  patients  notice  any  hindrance  in  movement.  This 
occurs  in  the  exudative  as  well  as  in  the  dry  form.  In  the  latter  we  find  a 
\-<ty  characteristic  ulnar  abduction  of  the  basic  joint  of  the  fingers  from  the 
firsl  to  the  fourth.  An  attempt  has  been  made  to  explain  this  by  contractures 
of  the  muscles  or  from  the  flaccid  condition  of  the  capsule;  this,  however,  I 
believe  to  be  incorrect.  For  in  older  persons  this  is  frequently  the  first  symp- 
tom noted,  even  before  there  is  any  abnormal  distention  of  the  capsule  or  any 
muscular  contractions.  It  is  more  reasonable  to  assume  that  the  lumbricales 
atrophy  simultaneously  with  the  interos-ei.  which  normally  have  the  property 
of  adduction,  besides  that  of  extension  of  the  basal  phalanx.  Later  this  devia- 
tion terminates  in  well  marked  subluxation.  That  the  bones  take  part  in  the 
atrophy  is  well  known;  in  the  senile  monoarthric  deforming  variety  this 
begins  in  the  end  of  the  joint;  hut  in  the  juvenile  polyarthritic  form  the 
Röntgen  picture  often  shows  a  conspicuous  coalescence  and  disappearance  of 
the  spongiosa  in  the  neighborhood  of  the  affected  joint.  Perhaps  this  is  the 
effeel  of  immobilization.  But  since  Sudeck  has  shown  that  in  every  form  of 
arthritic  inflammation,  distortion  of  trauma  may  produce  within  a  few  weeks 
decided  atrophy  of  the  hone-,  t  ran-ient  or  permanent,  similar  conditions  should 
also  lie  looked  for  in  chronic  arthritis.  The  shin  and  its  structures  take  part 
in  the  process,  and  Herz  ha-  described  a  case  in  which,  with  every  new  attack. 
a  glove-like  desquamation  of  the  skin  of  the  hand  and  shedding  of  the  nails 
occurred;  such  cases  are  rare.  The  changes  resembling  scleroderma  are  more 
frequenl  ;  the  shining  ivory-like  -kin  adheres  to  the  deformed  joint,  .-month 
and  immovable.  In  the  juvenile  cases  there  is  frequently  an  excessive  func- 
tional Hyperhidrosis.  The  contractures  which  occur  particularly  in  the  flexor 
muscles  of  the  fingers  and  toe-  are  important,  hut  these  may  also  he  noted 
in  the  extensor  groups  which  are  to  a  high  degree  responsible  for  the  terrible 
and  incurable  deformities  in  some  of  which  the  knees  are  drawn  up  to  the  chin. 
Frequently  the  tendons  and  tendon  sheaths  are  involved  in  the  process  and 
along  these  structures  tougb  subcutaneous  nodule-  occasionally  appear  which 
may  he  temporary  or  permanent;  these  are  also  noted  in  acute  rheumatism 
(see  a  dissertation  by  Rabinowitsch).  Pribram  asserts  that  he  has  only  ob- 
served them   in  acute  rheumatism;   Fig.  <>,  however,  i-  an  example  of  such 

nodule-  in  a  ca-e  of  undoubted  chronic  polyarticular  arthritis. 

In  conclusion.  I  must  mention  intermuscular  or  intramuscular,  dense,  cal- 
lous infiltrations  which  are  rarely  alluded  to  in  literature,  hut  are  well  known 
to  Orthopedists  and    masseurs,  and   arc  skilfully   treated    by   them. 

The  visceral  complications  an'  especially  interesting  on  account  of  their 
importance  in  the  conception  of  the  disease.  That  the  endocardium  may  he 
attacked  ha-  been  admitted,  and  the  frequency  with  which  this  happen-  varies 
in  ditl'ereiii  reports  from  I  per  cent.  t<>  so  per  cent,  of  the  ca-e-.  The  second- 
ary and  the  senile  deforming  varieties  do  not  attack  the  heart.  In  the  statis- 
tics of  primary  chronic  polyarthritis  there  are  differences  of  opinion  a-  to 
whether  functional  heart  murmur-  or  only  the  genuine  Valvular  affections  have 

keen  included.    Pribram,  who  was  the  first  to  call  attention  to  tin-  variation, 


252 


CHRONIC  ARTICULAR  RHEUMATISM 


gives  the  following  statistics  of  his  cases.  In  the  forms  beginning  acutely, 
there  were  53.4  per  cent,  of  heart  murmurs  and  20  per  cent,  of  valvular 
disease;  in  cases  chronic  from  the  outset  only  13.5  per  cent,  of  heart  murmurs 
and  4  per  cent,  of  valvular  disease. 

Chronic  nephritis  of  benign  character  and  showing  but  slight  tendency  to 
uremia  is  not  infrequently  observed. 

Among  other  complications  those  affecting  the  eye,  such  as  iritis,  iridocy- 
clitis and  episcleritis,  and  the  skin  (various  forms  of  erythema,  eczema,  urti- 
caria and  psoriasis)  are  to  be  mentioned.  The  occurrence  of  multiple  sym- 
metric lipomata  has  frequently  been  observed  in  connection  with  chronic 
arthritis,  as  well  as  bronchial  asthma,  dyspepsia,  hemorrhoids  and  numerous 
nervous  disturbances,  and  this  gives  rise  to  some  confusion.  These  affections 
are  spoken  of  particularly  by  authors  who  look  upon  chronic  arthritis  as  an 
expression  of  a  general  constitutional  anomaly. 

Lancereaux,  in  1870,  divided  rheumatism  into  two  classes,  of  which  one, 
"  qui  ne  laisse  jamais  des  traces  sur  son  passage  "  corresponds  to  acute  articular 
rheumatism ;  the  other  he  said  was :  "  pas  une  maladie,  mais  un  syndrome, 


Fig.  6. — Subcutaneous  Nodules  Situated  upon  the  Dorsal  Tendon  Sheaths  in  a  Case 
of  Chronic  Exudative  Polyarthritis  in  a  Young  Girl. 


une  manifestation  d'un  etat  constitutionel,"  "  le  branche  d'un  grande  famille 
pathologique,"  "  herpetisme"  a  vasomotor  trophic  neurosis,  expressing  itself 
in  dynamic  (migraine,  epistaxis,  neuralgias)  and  material  disturbances  in  the 
skin  and  of  the  tissues  deficient  in  blood-vessels.  In  this  group  is  also  included 
the  triad  of  diabetes,  obesity,  and  gout.  Bouchard  gives  a  similar  definition 
of  "  arthritisme  " ;  both  authors  emphasize  its  conspicuous  family  and  hered- 


CLINICAL  SYMPTOMS 


253 


itary  character,  and  even  so  careful  an  observer  as  Potain  believes:  "  Ce  n*est 
pas  telle  ou  telle  forme  de  rheumatisme  qui  se  transmet,  mais  une  predisposi- 
tion generale  exposant  ä  un  groupe  commun  d'affections  dans  laquelle  il  fant 
meme  ranger  la  goutte." 

On  this  point  it  is  difficult  to  arrive  at  a  definite  conclusion.     When  we 
read  the  clinical  reports  of  German,  French,  English  and  American  authors 


Fig.  7. — Patellar  Cartilage  of  a  Young  Max  \\ih>,  afteb  Passing  Through  \n  Attack 
of  Gout,  Succumbed  to  Croupous  Pneumonia.  The  cart ilage  shows  a  velvety  fibrilla- 
tion of  the  matrix  similar  to  the  condition  in  chronic  arthritis.  The  joints  contained  no 
deposits  of  urate  salts. 


we  receive  the  impression  thai  certain  forms  of  chronic  polyarthritis  frequently 
attack  debilitated  persons.  One  author  has,  however,  gathered  his  clinical 
material  in  the  hospital,  among  feeble,  anemic,  poorly  nourished  patients, 
cases  of  true  arthritis  pauperum,  whereas  the  cases  of  others  were  among  those 
living  in  affluence,  the  portion  of  the  population  debilitated  by  luxury  and 
close  intermarriage. 

under  >u*-\\  conditions  we  cannot  regard  the  simultaneous  appearance  of 
two  or  more  diseases  as  a  proof  of  their  identity,  and  since  decisive  statistics 

are  not  to  be  bad,  the  critical  -kepticiHii  of  A.  Holl'niann  ami  other  German 
authors   IS  certainly  just  ified. 

Yet  the  relation  of  arthritis  to  apparently  dissimilar  affections — and  here 
1  must  mention  psoriasis — becomes  constantly  more  obvious.  Adrian  has  re- 
cently reported  94  cases  of  this  combination,  which  has  been  known  in  Prance 
for  some  time.    Gerhardt  was  the  first  to  observe  the  condition  in  Germany, 


Fig.  8. — Radiograph  of  the  Hand  of  a  Gouty  Patient.  At  the  point  marked  by  the 
asterisk,  gouty  tophi  are  seen  as  translucent  foci;  at  the  dagger,  exostoses  similar  to  Ileb- 
erden's  nodes;  at  the  double  dagger,  subluxation  in  the  basal  joint  of  the  little  finger. 


CLINICAL  SYMPTOMS  255 

and  after  a  critical  analysis  he  came  to  the  conclusion  that  coincidence  can 
be  wholly  excluded,  since  in  his  and  other  cases  the  affections  show  simul- 
taneous exacerbations  and  improvement. 

Ih'iv.  also,  the  relation  existing  between  chronic  arthritis  and  gout  must 
be  considered.  This  much  is  certain:  1.  That  after  gout  has  existed  for  a 
long  time  in  a  joint,  proliferation  of  the  cartilage,  exostoses  and  disappear- 
ance of  the  capsules  are  found;  2.  That  atypical  gout  may  give  rise  to  poly- 
articular swelling,  resembling  the  exudative  form  of  arthritis ;  3.  That  in  gouty 
families,  individuals  may  present  symptoms  resembling  chronic  arthritis. 
But  if  we  do  not  wish  to  lose  ourselves  in  a  realm  of  unfruitful  speculation, 
we  must  adhere  to  the  belief  that  gout  is  an  affection  characterized  by  n 
deposit  of  uric  at  id  sails  in  Ihr  body  and  by  tin'  presence  of  uric  acid  in  the 
blood.  The  latter  point  will  decide  the  differential  diagnosis  of  doubtful 
cases,  in  which  we  should  place  our  dependence  not  upon  the  uncertain  thread 
test  of  Garrod.  but  upon  the  more  difficult  chemical  analysis. 

We  may,  therefore,  look  upon  gout  as  one  of  the  causes  of  chronic  arthritic 
changes,  while  recognizing  that  the  two  diseases  are  by  no  means  identical. 

The  constitutional  predisposition  appears  to  be  of  especial  importance  in 
one  form  of  chronic  arthritis,  namely,  that  marked  by  Eeberden's  nodi--. 
They  are  found  isolated,  especially  in  the  aged,  and  then  are  frequently  hered- 
itary; very  often  they  are  associated  with  asthma,  migraine,  neuralgia,  sciatica 
and  muscular  rheumatism  and  particularly  with  gout.  Bouchard  was  the  first 
to  describe  nodosities  of  the  middle  joints  of  the  fingers  due  to  swelling  of 
the  second  phalanx  and  occurring  in  cases  of  gastric  dilatation;  he  gave  them 
the  name  of  " comptodactylie,"  and  showed  that  this  swelling  disappeared 
with  improvement  in  the  gastric  affection.  Pribram  also  observed  one  case 
of  this  malady. 

I  do  not  believe  that  it  will  be  possible  hereafter  to  deny  the  existence 
of  a  constitutional  arthritis;  hut  it  i-  not  necessary  to  adopt  the  scheme  of 
the  French,  who  look  upon  every  non-infectious  arthritis  a-  an  expression  of 
an  "herp6tisme  or  arthritisme."  In  the  future  accurate  weighing  of  all  the 
circumstances  will  show  whether  definite  anatomical  Lesions  exist  or  an  arthrit  i- 
runs  a  particular  course  in  persons  with  a  predisposition  of  the  type  described 
by  the  French. 

The  infectious  theory  of  arthritis  has  many  more  supporters  than  has 
dyscrasia.  The  febrile  form  which  comes  in  paroxysms  with  a  relatively 
frequent  endocarditis  ami  severe  general  disturbances  gives  strong  suppori  to 
this  view,  ami  on  several  occasions  microorganisms  have  been  cultivated  (by 
M.  Schiiller,  Bannatyne,  Blaxall  ami  Wohlmann)  from  the  content-  of  the 
joint  ami  their  pathogenicity  has  been  proven  by  animal  experiment,  un- 
fortunately, the  microorganisms  described  are  not  all  the  Bame,  and  bo  careful 
an  investigator  a-  Pribram  found  it  impossible  to  detect  any  of  them  in  the 
cases  he  examined.  The  pathogenic  agent,  therefore,  as  in  the  ca-e  of  articular 
rheumatism.  i>  not  yet  determined  and  the  infection-  nature  of  the  disease 
i-  only  a  hypothesis,  although  a  very  probable  one. 

A-  a  third  possibility,  disease  of  the  central  nervous  system  has  I □  con- 
sidered.   This  i-  suggested  by  the  symmetry  of  the  affection,  the  atrophy  and 


256  CHRONIC  ARTICULAR  RHEUMATISM 

contractures  of  the  muscles,  the  trophic  cutaneous  disturbances,  and  the  simi- 
larity of  the  chronic  rheumatic  joint  changes  to  unmistakable  nervous  arthrop- 
athies occurring  in  tabes,  syringomyelia,  progressive  muscular  atrophy,  hemi- 
plegia, progressive  paralysis  and  also  in  peripheral  neuritis.  In  the  latter 
disease  rarefaction  of  the  bony  substance  with  swelling  of  the  distal  ends  of 
the  extremities  and  the  formation  of  club  finger  tips  is  observed  (pulmonary 
osteoarthropathy  of  P.  Marie,  see  the  compilation  of  W.  Berent).  In  diseases 
of  the  central  nervous  system  disfiguring  deformities  appear  with  atrophy  and 
proliferation  of  the  bones  and  cartilage,  and  these  show  a  great  resemblance 
to  senile  monoarthritis,  differing,  however,  by  their  more  rapid  course,  absence 
of  pain,  fissures  in  the  capsule,  and  extra-capsular,  osseous  and  cartilaginous 
proliferations. 

To  explain  the  muscular  atrophy  the  assumption  of  a  primary  nervous 
affection  is  quite  unnecessary,  since  Charrier  has  shown  that  this  atrophy 
accompanies  all  joint  inflammations,  especially  when  they  run  their  course 
with  effusion  (Kremer).  Hoff  a  proved  that  they  do  not  occur  when  the 
centrifugal  nerves  are  severed;  they  are,  therefore,  trophoneuroses  which  are 
produced  by  reflex  action  initiated  by  the  diseased  joint  surfaces. 

As  anatomical  investigation  of  the  spinal  cord  has  given  positive  results 
only  in  rare,  exceptional  cases  (R.  Wichmann)  the  neurotic  explanation  seems 
scarcely  probable.  Under  certain  circumstances,  some  forms  of  arthritis  might 
be  looked  upon  as  infectious  trophoneuroses,  following  Teissier  and  Roque. 

It  is,  however,  quite  unlikely  that  the  various  forms  of  chronic  articular 
rheumatism  are  due  to  any  single  cause.  In  the  first  place,  we  may  exclude 
monoarthritis  deformans,  which  is  so  closely  allied  to  other  senile  changes 
(Weichselbaum)  and  which  is  so  frequently  produced  by  trauma.  But  it  is 
also  unlikely  that  there  is  any  one  cause  for  all  cases  of  chronic  polyarthritis, 
if  we  bear  in  mind  the  forms  which  are  similar  in  all  these  symptoms,  and 
yet  are  produced  by  various  well  known  and  quite  distinct  infectious  diseases. 
Gerhardt  in  1896  originated  the  term  acute  rheumatoid  or  pseudo-articular 
rheumatism,  and  defined  it  as  follows :  "  Pseudo-articular  rheumatism  is  that 
form  of  disease  in  which  it  may  be  proven,  or  where  it  is  very  likely,  from 
its  external  appearance,  that  it  is  produced  by  the  special  pathogenic  organ- 
isms of  a  definite  infectious  disease;  the  remaining  cases  are  included  under 
true  articular  rheumatism."  These  pseudo-rheumatisms  have  in  common  that 
they  occur  only  in  a  minority  of  the  individuals  who  are  attacked  by  the 
infection  in  question  and  that  the  same  organism  which  produces  the  infectious 
disease  also  produces  joint  pain,  arthritic  swelling  or  suppuration  of  the  joint. 
In  this  sense  we  may  speak  of  chronic  rheumatoid  ("pseudo-rheumatism"  of 
Pribram)  as  an  arthritis  in  which  the  exciting  cause  is  one  of  the  acute 
exanthemata,  influenza,  or  pneumococcus  infection,  particularly  gonorrhea, 
syphilis  and  tuberculosis.  Gonorrhea  is  a  clear  example  of  the  fact  that  the 
same  microorganism,  according  to  its  virulence  and  the  individual  constitu- 
tion of  the  affected  person,  may  cause  any  grade  of  the  disease  from  a  transi- 
tory arthritic  pain  and  serous  effusion  to  an  incurable,  chronic  deforming 
arthritis  and  spondylitis.  I  should  like  to  call  particular  attention  to  rheu- 
matic tuberculoid  or  tuberculous  rheumatoid,  a  condition  which  lately  has  been 


TREATMENT  257 

frequently  described  (Poncet.  Maillard,  II.  Strauss.  Barjon.  Koma,  Potal). 
The  usual  <our-e  of  such  cases  is  this:  the  disease  begins  as  a  subchronic  or 
chronic  articular  rheumatism  which  finally  becomes  localized  to  one  or  more 
joints,  and  there  develops  typical  tuberculous  changes.  This  course  resembles 
osteomyelitis j  of  which  we  observed  a  case  in  the  clinic  at  Basel  in  an  indi- 
vidual aged  seventeen,  in  whom,  after  a  fever  lasting  several  months,  accom- 
panied with  wandering  multiple  joint  swellings,  muscular  contractures,  and 
exostoses,  the  epiphyses  became  loosened  from  the  neck  of  the  left  femur, 
thus  confirming  the  diagnosis. 

True  chronic  polyarthritis  may  owe  it-  origin  to  various  infections,  or  to 
constitutional  causes  of  the  type  suggested  by  Lancereaux  and  Bouchard. 
Perhaps  in  some  cases  nervous  disturbances  may  play  a  role.  These  cases 
cannot  be  diagnosed  by  rules,  no  matter  how  skilful  the  reasoning  processes, 
but  only  by  following  the  advice  given  by  Archibald  Garrod,  to  inquire  into 
the  family  history  of  each  individual  case,  its  nervous  disturbances,  etc.,  and 
by  carefully  investigating  the  bacteria  present.  Perhaps  in  tins  manner  a 
rational  differentiation  of  the  varying  forms,  which  to-day  is  impossible,  may 
in  time  be  attained. 

TREATMENT 

As  in  all  chronic  diseases  for  which  we  have  no  specific,  the  number  of 
remedies  is  legion.  But,  in  giving  a  synopsis,  I  shall  divide  them  into 
groups. 

First,  liih  riml  remedies.  I  take  for  granted  the  knowledge  that  the  anti- 
rheumatics, the  salicylates,  antipyrin  and  allied  remedies  often  diminish  pain, 
but  never  have  the  specific  action  which  is  the  case  in  acute  articular  rheuma- 
tism. The  salts  of  iodin  are  very  useful,  not  only  in  gonorrheic  and  syphilitic 
rheumatoid,  but  also  in  the  exudative  polyarthritic  form.  Tonics  are  advised 
by  the  besl  authorities,  and  since  experience  has  shown  that  in  these  affections 
the  local  difficulties  are  closely  related  to  the  general  health  of  the  patient, 
cod  liver  oil,  iron,  arsenic,  quinin  and  Btrychnin  preparations  are  of  decided 
benefit  in  anemic,  feeble,  emaciated  individuals,  especially  after  febrile  parox- 
ysms or  after  active  treatment.  The  salts  of  lithia,  and  mineral  waters 
containing  lithia,  have  been  advised  on  account  of  their  action  in  gout,  but 
there  is  do  rational  indication  here  for  their  use.  In  fact,  in  a  disease  in 
which  excessively  chronic  and  decided  vet  spontaneous  changes  occur,  the 
value  of  any  curative  agenl  is  always  very  uncertain. 

M'ii/rr'-  successful  trials  of  streptococcus  serum,  which  were  based  upon 
the  theory  of  an  infectious  etiology,  are  interesting  but  by  no  mean-  con- 
clusive. 

The  principal  pole  in  therapy  is  played  by  external  physical  remedi 

Water  musl  be  mentioned  first.  Thai  energetic  applications  of  cold  water 
are  harmful  in  the  first  stages  of  inflammation  is  a  common  experience. 
Only  after  acute  exacerbations  have  run  their  course,  and  after  long  continued 
Bweating  procedures,  may  cold  douche-,  1 die  baths,  and  affusions  be  made  u-o 

of  by  an  experienced  and  careful   hand,  and   then   serve  a   ii-eful    purpose  a-  a 

hardening  pro, 


258  CHRONIC  ARTICULAR  RHEUMATISM 

Warm  water  in  all  forms  is  frequently  employed,  from  the  Priessnitz  pack 
to  a  hot  bath.  The  latter  are  used  particularly  in  the  form  of  natural  springs, 
which  are  of  ancient  repute.  Their  effect  is  to  be  ascribed  more  to  the  tem- 
perature of  the  water  and  the  duration  of  the  bath  than  to  the  chemical 
constituents  of  the  water  (hydrogen  sulphid,  alkaline  sulphates,  calcium,  gyp- 
sum, sodium  chlorid,  etc.).  In  rheumatism,  the  unaccountable  experience  is, 
that  natural  mineral  waters  may  bring  about  improvement  after  the  effect 
of  hot  water  baths  in  the  home  has  been  exhausted.  This  effect  is  chiefly  due 
to  the  cutaneous  irritation  of  mineral  waters  rich  in  carbonic  acid,  such  as 
those  of  Nauheim  and  Oeynhausen,  or  of  mud  baths  combined  with  the  thermic 
effect  of  the  water.  To  these  must  be  added  the  effect  of  applications  of  peat- 
soil,  fango,  natural  sulphur,  etc.,  and  heat  applied  in  various  ways,  sweat 
procedures,  hot  air  and  steam  douches  (the  latter  often  producing  a  relaxa- 
tion of  muscle  contractures  and  stiffness),  sand  baths,  local  and  general  hot 
air  baths  and,  finally,  local  inflammatory  applications ;  painting  with  tincture 
of  iodin  or  ichthyol,  compresses  with  iodin — potassium  iodid  salve  (1 :  10  :  100), 
vesication,  etc. 

All  these  applications  have  in  common  a  tendency  to  produce  hyperemia, 
and  August  Bier  has  contributed  other  original  therapeutic  methods.  The 
irritating  or  anodyne  effect  of  derivatives  and  counterirritants  has  always 
been  explained  on  the  hypothesis  that  the  blood  is  drawn  from  the  distant 
diseased  parts  to  the  surface.  Bier  has  shown  that  this  is  incorrect;  that,  on 
the  contrary,  the  deeper  parts  partake  in  the  hyperemia,  and  that  this  produces 
the  anodyne  and  absorbent  effect.  Bier  stimulates  this  action  still  further  by 
hot  air  and  stasis.  The  former  produces  an  intense,  highly  active,  i.  e., 
arterial,  hyperemia,  which  is  greater  the  higher  the  temperature  of  the  agent. 

A  simple  apparatus,  a  wooden  box  with  two  openings  to  permit  the  en- 
trance and  the  exit  of  the  hot  air,  and  bandages  on  which  to  rest  the  affected 
member  are  sufficient  for  the  purpose;  the  hot  air  is  produced  by  a  Quincke 
sweat  tube,  or  a  phenix  ä  air  eh  and,  the  tube  being  introduced  into  the  open- 
ing of  the  box.  Similar  apparatus  has  been  employed  by  Tallermann,  and 
Lindemann  has  used  electric  heat;  the  effect  of  the  electric  light  batlis  now 
in  vogue,  in  which  the  electric  bulbs  radiate  not  only  light  but  heat,  is  the 
same.  For  institutions  these  are  very  serviceable,  as  they  are  not  dangerous 
and  are  easy  to  regulate.  Bier's  apparatus,  however,  has  the  enormous  advan- 
tage that  it  may  be  constructed  by  a  carpenter,  at  very  slight  cost,  in  the 
house  of  the  patient,  and  be  employed  at  the  bedside.  The  effect  of  this  remedy 
is  excellent,  as  I  am  able  to  testify. 

The  value  of  passive  hyperemia  attracted  the  attention  of  Bier  on  account 
of  the  rarity  with  which  tuberculosis  of  the  lungs  is  found  associated  with 
valvular  disease  of  the  heart.  He  attempted  artificial  blood  stasis  in  tubercu- 
losis of  the  joints,  and  was  so  gratified  with  the  success  attained  that  he 
employed  this  method  also  in  other  joint  diseases.  Above  the  diseased  area 
an  elastic  (rubber)  bandage  is  applied  so  tightly  that  the  extremity  becomes 
edematous. 

However,  the  pressure  must  not  be  so  great  as  to  compress  the  arteries; 
the  member  must  be  warm,  and  the  stasis  must  not  produce  the  slightest  pain. 


LITERATURE  259 

The  compression  may  be  continued  for  a  long  time.  I  have  carried  on  this 
treatment  for  several  months  at  a  time.  Bier  has  lately,  however,  advised 
us  to  use  the  method  for  only  one  or  two  hours  daily. 

The  effect  is  at  first  to  decrease  the  pain  to  such  a  degree  that,  for  example, 
the  tearing  pains  of  gonorrheal  arthritis  soon  cease,  giving  way  to  a  feeling 
of  well-being. 

The  rule  which  Bier  has  expressly  emphasized  is  this,  that  the  stasis  itself 
must  never  produce  pain;  as  soon  as  this  appears,  the  bandage  must  be 
Loosened  or  removed. 

The  further  effect  of  stasis  is  to  increase  absorption.  It  is  evident  at 
once  that  joint  effusion,  edematous  infiltrations  of  the  capsule,  and  prolifera- 
tion of  the  joint  villi  are  more  amenable  to  some  treatment  than  are  ecchon- 
droses  and  osteophytes,  that,  therefore,  the  dry  atrophic  form  of  chronic 
arthritis  is  less  susceptible  to  treatment  than  the  hypertrophic  proliferating 
forms  with  their  spindle-shaped  joints.  Bier's  hot  air  and  stasis  treatment, 
judged  by  the  results,  is  by  no  means  a  panacea.  The  physician  treating  a 
case  of  chronic  rheumatism  must  decide  which  symptoms  most  urgently  call 
for  relief.  Fresh  joint  and  capsule  swellings  require  rest,  the  alleviation  of 
pain,  and  the  application  of  remedies  which  increase  absorption,  such  as  the 
salicylates,  iodin,  and  heat.  Older  capsular  contractures,  in  which  immobility 
and  fibrous  ankylosis  have  occurred,  require  active  and  passive  movements  and 
the  condition  is  often  relieved  by  stasis.  Muscular  atrophy  is  benefited  by 
faradic  treatment  and.  above  all.  by  massage.  Contractures  require  applica- 
tion- of  heat,  prolonged  baths,  hot  air  or  steam  douches,  peat  or  fango  poul- 
tices,  and  protect  ion  from  cold. 

Tlie  earlier  the  treatment  is  begun,  the  better  the  result. 

Firm  ankyloses  and  hyperostoses,  particularly  of  the  larger  joints,  require 
surgical  and  orthopedic  treatment:  practice  with  suitable  apparatus  may  im- 
prove the  gait,  and  prevent  the  bad  consequences  of  too  -reat  weight  upon 
the  vertebral  column.  The  operative  treatment  of  mono-  ami  polyarthritis. 
according  to  the  few  results  reported  by  W.  Müller  and  his  pupil  Elter. 
deserves  further  trial. 


LITERATURE 

A   very  complete  compilation  has  recently  been  given  by  Pribram  in  Nothnagel'» 

Handbuch,  vii,  2. 
('.  Adrian,  "Ueber   Arthropathia   psoriatica."    Grenzgebiete  der  Median,  L903,  \i. 

p.  237. 
W.  Anschuht,  "Ueber  die  Versteifung  der  Wirbelgelenke."    Grenzgebiete  der  Median, 

viii,  p.   HU . 
Bannatyne,  Wohlmann  and  Blaxaü,  f. nun/,  25,   \pril.  1896. 
Barjon,  "Radiographic  appliquee  ä  L'dtude  des  arthropathies  d&ormantee,"  Paris, 

L897. 

terew,    " Steifigkeit    der    Wirbelsaule."    Neurologisches   Centralbl.,    1893,    und 

Zeit8chr.  /.  Naturheükunde,  1899,  w. 
Beer,  "Rigidität  der  Wirbelsäule."     Wiener  ""</.  Bhuur,  iv>;,  \r.  s  u.  <). 


260  CHRONIC  ARTICULAR  RHEUMATISM 

W.  Bereut,  "Zur  Aetiologie  osteoarthropathischer  Veränderungen."  Berliner  klin. 
Wochenschr.,  1903,  Nr.  4. 

A.  Bier,  "Hyperämie  als  Heilmittel,"  Leipzig,  1903;  ferner  19.  Congress  für  innere 
Mediän  in  Berlin,  1901;  Münchener  med.  Wochenschr.,  1S9S  und  1901,  Nr.  48. 

Bouchard,  "Lecons  sur  les  autointoxications,"  1887. 

/.  Braun,  "Klinische  und  anatomische  Beiträge  zur  Kenntnis  der  Spondylitis  de- 
formans," Hannover,  1875. 

R.  Cassirer,  "Ueber  myogene  Wirbelsteifigkeit."  Berliner  klin.  Wochenschr.,  1902, 
Nr.  10  u.  11. 

Charrin,  " Progres  Med.,"  1S94. 

/.  /.  Clarke,  "Note  of  a  Painful  Condition  of  the  Twelfth  Pair  of  Ribs."  Clinical  Soc. 
of  London,  October  11,  1902. 

H.  Curschmann,  "Berichte  der  med.  Gesellschaft  zu  Leipzig."  Schmidt's  Jahrbücher, 
1895. 

G.  Lavaine,  "Etude  comparee  du  rheum,  art.  aigu.  et  des  poussees  aigues  du  rheum. 
chronique."     These,  Paris,  1897. 

J.  Elter,  "Weitere  Beiträge  zur  chirurgischen  Behandlung  der  Arthritis  deformans." 
Zeitschr.  f.  Chirurgie,  1903,  66,  p.  387. 

Sir  Alfred  Garrod,  "Natur  und  Behandlung  der  Gicht."  German  by  Eisenmann. 
Würzburg,  1861. 

Archibald  Garrod,  "Clinical  and  Pathological  Relations  of  the  Chronic  Rheumatic 
Affections."     Lancet,  March  16,  1901. 

C.  Gerhardt,  "Ueber  Rheumatoidkrankheiten."  14.  Congress  für  innere  Mediän  in 
Wiesbaden,  1896,  p.  169.  "Verhältnis  der  Schuppenflechte  zu  Gelenkerkrankun- 
gen."    Berliner  klin.  Wochenschr.,  1894,  Nr.  38. 

A.  Hoffman,  "Lehrbuch  der  Constitutionskrankheiten,"  Stuttgart,  1893. 

Herz,  "Ueber  das  gleichzeitige  Vorkommen  von  chronischen  Haut-  und  Gelenker- 
krankungen."    Wiener  Hin.  Wochenschr.,  1S96,  Nr.  26. 

II uff a,  "Zur  Pathogenese  der  arthritischen  Muskelatrophien."  Volkmann' 's  Sammlung 
Hin.  Vorträge,  1X92,  N.  F.,  Nr.  50. 

M.  Kachel,  "Untersuchungen  über  Polyarthritis  chronica  adhsesiva."  Ziegler's 
Beiträge,  1903,  xxxiii,  p.  327. 

0.  Kremer,  "  Pathogenese  der  arthritischen  Amyotrophies"  Inaug.-Diss.,  Greifswald, 
1902. 

Lancereaux,  "Atlas  d'anatomie  pathologique,"  Paris,  1871.  " Traite  de  l'herpetisme, " 
Paris,  1883;  "  Lecons  de  Clinique  medicale,"  1892,  I. 

Landre-Beauvais,  "Doit-on  admettre  une  nouvelle  espece  de  goutte  sous  le  nom  de 
goutte  asthonique  primitive?"     These,  Paris,  an  viii  (1800). 

Lindemann,  "Locale  Behandlung  von  Gelenkrheumatismus,  etc.,  mit  elektrischen 
Heissluftapparaten."     Therapeut.  Monatshefte,  März,  1900. 

L.  Maülard,  "Rheumatisme  tuberculeux."     Gazette  hebdomad.,  1900,  No.  88. 

K.  M anasse,  "Zwei  Fälle  von  isolirter  rheumat.  Erkrankung  der  Kiefergelenke. '' 
Münchener  und.  Wochenschr.,  1902,  Nr.  20. 

Menzer,  Deutsche  med.  Wochenschr.,  1903,  Nr.  67  und  Zeitschr.  f.  klin.  Mediän,  47, 
p.  109. 

Joh.  Müller,  "Beobachtung  über  reine  Zwerchfell-Bauchathmung  bei  ankylosirender 
Wirbelgelenkentzündung."     Verhandlungen   der    Würzburger   phys.-med.    Gesell- 
schaft, 1901,  p.  41. 
W.  Müller,  "Zur  Frage  der  operativen  Behandlung  der  Arthritis  deformans."    Archiv 
f.  klin.  Chirurgie,  47,  1894. 


LITERATURE  261 

Pribram,  "Chronischer  Gelenkrheumatismus  und  Osteoarthritis  deformans."    Noth- 
nagel'8  Handbuch  der  spec.  Pathologie  und  Therapie,  vii,  2. 
E.  Pfeiffer,  "Ueber  Gichtfinger."     Berliner  Min.  Wochenschr.,  1891,  Nr.  15. 
Potain,  Semaine  med.,  20.  Mai,  1S91,  p.  210. 
A.  Poncet,  "  Rheumatisme  tuberc.  abartieulaire."    Lyon  med.,  1902,  No.  29;  Gazette 

hebdomad.,  1902,  Nr.  58. 
Potal,  "Rheum.  artic.  tub.  chronique."    Gazette  hebdomad.,  1902,  No.  10. 
//.  Rabinowüsch,  "Beitrage  zur  Kenntnis  des  Gelenkrheumatismus  mit   Knötchen- 

bildung."    Jnaug.-Diss.,  Berlin,  1899. 
Roma,  "Rheumat.  tuberculeux."    Gazette  hebdomad.,  1902,  No.  93. 
Roese,  "Ueber  amyloidentartung  bei  chronischer  Arthritis."    Inaug.-Diss.,  Leipzig, 

1 897. 
Schur/, an/t,    '•Krankheiten    der    Knochen    und    Gelenke."     Deutsche    Chirurgie,   28. 

Liefen  mi:-. 
.1/.  Schüller,  Berliner  Min.  Wochenschr.,  1893,  Nr.  36,  1900,  Nr.  5  bis  7:    15.  Congress 

für  in mn  Malirin,  Berlin,  1897. 
Schlesinger,  "Chronische  Steifigkeit  der  Wirbelsäule."    Grenzgebiete  der  Medicin,  1900. 
Senator,    "Krankheiten    der    Bewegungsorgane."    Ziemssen's    Handbuch    der    spec. 

Pathologie,  xiii. 
Sudeck,    "Acute    (trophoneurotische)    Knochenatrophie    nach   Entzündungen   und 

Traumen  der  Extremitäten."    Deutsche  med.  WochenschfT,  1902,  Nr.  19. 
//.  Strauss,  "Acute  Miliartuberculose  unter  dem  Bild  einer  Polyarthritis."     Charüi- 

Annalen,  xxiv. 
Tattermann  und  Mendelsohn,  "Behandlung  <h'>  chronischen  Gelenkrheumatismus." 

Deutsche  med.  Wochenschr.,  1898,  Nr.  11. 
Ti  i  ■■■  i'  r  et  Roque,  "  Rheumatisme  chronique."    Traite"  de  m^d.  de  Brouardel.     Gilbert 

et  Girode. 
Trousseau,  "Clinique  m&licale." 

/.'.  r.   Volkmann,  "Krankheiten  der  Gelenke."    "Pitha-Billroth 'sehe  Chirurgie." 
Vidal,  "Considerations  sur  le  rheum.  chron.  primitiv."     These,  Paris,  L855. 
Weichselbaum,   Virchow's  Archiv,  lv. 
Wohlmann,  Brit.  Med.  Jour.,  November  11,  19 


PENTOSURIA 

By    F.    BLUMENTHAL,    Berlin 

Prior  to  the  last  few  years  all  urine  which  gave  a  distinct  and  unquestion- 
able reduction  test  was  considered  to  contain  sugar,  and  permitted  us  to  con- 
clude the  presence  of  grape  sugar;  this  view  is  no  longer  tenable.  We  know 
now  that  a  variety  of  sugars  are  found  in  human  urine  all  of  which  react  to 
the  recognized  sugar  tests  (Trommer's,  Nylander's,  the  Phenylhydrazin  test). 
Besides  grape  sugar  we  find  milk  sugar,  which  appears  during  the  puerperal 
period  in  a  woman  who  has  an  abundant  secretion  of  milk  yet  does  not  nurse 
her  child;  this  substance  may  persist  in  the  urine  for  months  post  partum, 
in  fact  as  long  as  the  secretion  of  milk  continues.  Here  the  differential  diag- 
nosis from  grape  sugar  is  accomplished  very  simply  by  the  fermentation  test; 
milk  sugar  does  not  ferment  with  yeast,  while  grape  sugar  does.  Eobinson 
and  Lepine,  and  also  Eosin  and  Laband,  have  lately  described  cases  of  levulo- 
suria  which  is  characterized  by  its  independence  of  the  ingestion  of  carbo- 
hydrates, and  this  condition  may  be  recognized  by  the  decided  levorotatory 
power  developed  during  the  fermentation  test  of  the  urine.  Of  less  impor- 
tance is  the  occurrence  of  maltose,  which  occasionally  appears  in  the  urine  in 
diseases  of  the  pancreas,  and  the  presence  of  which  can  scarcely  be  detected 
even  by  the  most  delicate  chemical  methods.  Of  more  importance  are  the  con- 
bined  glycuronic  acids  and  the  pentoses. 

We  refer  here  to  the  former  substances  because  the  combined  glycuronic 
acids  may  be  considered  as  pentose-carbonic  acids,  C5Hin05C02.  Combined 
glycuronic  acids  are  foimd  in  the  urine  after  the  administration  of  numer- 
ous drugs,  especially  such  as  contain  the  aldehyd  and  ketone  groups  ( Neu- 
bauer), and  these  may  then  be  excreted  in  the  urine  in  combination  with  gly- 
curonic acid.  Among  the  best  known  of  these  drugs  are:  morphin,  chloral, 
turpentine,  menthol,  antipyrin,  etc.  Glycuronic  acid  is  also  found  in  the 
urine  combined  with  indoxyl  and  with  phenol.  As  some  of  the  combined 
glycuronic  acids  respond  to  the  Trommer  and  Nylander  tests,  it  may  be  of 
importance  in  such  cases — particularly  with  doubtful  tests — to  search  for  the 
cause,  and  it  is  then  not  infrequently  found  that,  at  least  in  human  urine,  we 
are  dealing  with  a  very  decided  indicanuria.  If  the  patient  who  voids  this 
reducing  urine  has  taken  any  drug,  the  supposition  is  natural  that  it  has  been 
excreted  as  glycuronic  acid  and  has  thus  caused  the  reduction. 

The  urine  coming  from  a  case  of  pentosuria  gives  a  distinct  but  somewhat 
delayed  reaction  with  Trommer's  test,   and  usually    (as   E.    Salkowski   first 
263 


PENTOSURIA  263 

noted)  the  reduction  with  Trommer's  test  only  takes  place  upon  cooling,  but 
then  quite  suddenly. 

The  Phenylhydrazin  test  is  also  positive  with  pentose;  Nylander's  test  is 
not  quite  so  distinct,  and  thus  it  happens  that  a  person  applying  for  life 
insurance  is  sometimes  rejected  on  the  ground  that  he  is  supposed  to  be  a  dia- 
betic. This  happened  in  the  case  of  a  patient,  aged  thirty,  who  had  been  mar- 
ried for  but  a  short  time,  and  who,  on  account  of  his  rejection  for  life  insur- 
ance, was  very  unhappy.  In  great  excitement  he  consulted  a  physician  for  a 
probable  diabetes.  Upon  examination  of  the  urine  the  physician  at  once  be- 
came suspicious,  fur  the  urine  was  optically  inactive  in  the  polariscope  and 
did  not  ferment  with  yeast.  When  t he  urine  was  examined  more  accurately 
(Prof.  Salkowski)  it  was  found  that  the  sugar  it  contained  was  pentose. 

Here  was  a  case  in  which  the  examination  of  a  urine  having  reducing 
properties  but  optically  inactive  and  non-fermentative  led  to  the  discovery 
of  pentose;  the  question  may  quite  properly  be  asked,  "How  can  such  a  diag- 
nosis be  confirmed  with  certainty?  " 

A  urine  that  contain-  pentose,  and  only  such  a  one,  gives  the  orcix  test. 
This  is  done  in  the  following  manner:  3  c.c.  of  urine  are  decomposed  with 
about  (>  c.c.  of  fuming  hydrochloric  acid;  to  this  is  added  a  few  granules  of 
orcin  and  the  mixture  is  then  heated  to  the  boiling  point.  As  soon  as  the 
mixture  begins  to  boil,  a  bluish  green  color  appears  which  is  proof  positive  of 
pentose.  Orine  containing  grape  sugar  or  milk  sugar  doc-  no!  give  this  reac- 
tion; urine  containing glycuronic  acid  gives  the  tesi  only  upon  prolonged  boil- 
ing, and  then  the  precipitate  is  never  greenish  blue  but  more  of  a  violet 
color. 

Before  the  orcin  tesi  was  introduced  into  the  chemistry  of  urine,  the 
phloroglucin  test  was  used  hut  it  was  much  less  positive.  According  to  E. 
Salkowski,  tin-  tesi  may  be  carried  out  in  the.  following  manner:  :'.  c.C  of 
urine  are  decomposed  with  3  c.c.  of  hydrochloric  acid  of  a  specific  gravity  of 
L.019,  to  which  a  few  granules  of  phloroglucin  are  added  and  the  mixture  is 
heated  to  the  boiling  point.  Even  after  -light  heating  a  cherry  red  color 
develops  which  gradually  becomes  more  distinct,  and  anally  (a  point  that  is 
characteristic)  turn-  greenish  black.  If  amy]  alcohol  is  then  added,  and  the 
mixture  shaken,  the  coloring  matter  is  dissolved,  ami  -how-,  an  absorption 
hand  between  I»  and  K.  i.e..  between  yellow  and  green.  Drines  which  contain 
large  amount-  of  glycuronic  acid  -how  a  brownish  black  color,  but  presenl 
the  -ame  absorption  line--,  urines  which  contain  only  trace-  of  glycuronic 
acid  -how  no  absorption  line-  nor  the  characteristic  colors  indicative  of 
pentose. 

I  believe  that  the  orcin  teal   is  more  reliable  than  the  phloroglucin  \^--\. 

a-  mo-i  of  the  glycuronic  acids  yield  no  reaction  with  the  latter;  at  least,  ti"t 
if  the  tesl  i-  done  in  the  manner  I  have  indicated.  In  using  the  orcin  test, 
one  or  two  drop-  of  liq,  ferri  Besquichlor.  may  he  added,  according  to  Bial  ; 
tin-  produce-  a  beautiful  blue  color.  Or  l'>ial*s  reagent  may  he  used  (acid. 
muriat.  cone.  250.0;  orcin  0.5;  liq.  ferri  sesquichlor.  H>  drops).  Confusion 
with  pentose,  provided  the  urine  i-  examined  twenty-four  hour-  after  it  has 

been  voided,  is  only  possible  with  two  of  the  glycuronic  acid-  at  present  known. 


264  PENTOSURIA 

namely,  with  menthol  glycuronic  acid  and  turpentinglycuronic  acid.  Both  of 
these  glycuronic  acids  have  the  property  of  decomposing  spontaneously,  and  as 
free  glycuronic  acid  also  reacts  to  the  orcin  test,  they  may  be  confounded.  We 
are  prevented  from  making  this  mistake,  first,  by  the  history,  as  mentholgly- 
curonic  acid  and  turpentinglycuronic  acid  are, only  excreted  after  the  inges- 
tion of  menthol  and  turpentine;  secondly,  by  the  odor  of  the  urine;  menthol 
urine  smells  of  peppermint,  turpentine  urine  of  violets.  Therefore,  in  human 
urine,  since  the  introduction  of  the  orcin  test,  there  can  scarcely  be  any  diffi- 
culty in  the  recognition  of  pentose.  The  circumstances  are  different  in  the 
urine  of  the  herbivora.  They  frequently  take  up  with  their  food  a  mass  of 
pentosan,  that  is.  the  anhvdrid  of  pentose.  The  pentosans  have  the  same  rela- 
tion to  pentose  that  glycogen  has  to  grape  sugar.  These  pentosans  are  in  part 
excreted  as  such  and  give  the  orcin  test,  as  does  pentose,  for  by  heating  with 
hydrochloric  acid  pentose  is  developed  from  pentosan. 

As  the  urine  of  the  herbivora  very  frequently  has  reducing  properties  and 
therefore  gives  a  more  or  less  distinct  orcin  test,  confusion  with  pentose  is  not 
impossible.  In  these  cases  the  Phenylhydrazin  test  must  be  employed;  if  this 
is  positive  while  the  fermentation  test  is  negative,  pentose  is  present.  If  the 
fermentation  test  is  positive,  after  fermentation  has  ceased  the  Phenylhydrazin 
test  must  also  be  positive  if  pentose  is  present. 

After  this  slight  digression,  we  return  to  the  chemical  analysis  of  the 
urine.  If  we  have  under  consideration  a  urine  that  gives  a  positive  reaction 
with  Trommer's  test,  the  Phenylhydrazin  test,  the  orcin  and  phloroglucin  tests 
for  pentose,  if  the  urine  is  optically  inactive  and  does  not  ferment,  then  the 
patient  excreting  such  a  urine  has  pentosuria.  The  question  now  arises,  What 
does  this  condition  indicate?  As  it  is  certain  that  he  is  excreting  sugar,  i.  e., 
pentose,  there  is  unquestionably  a  disturbance  in  sugar  metabolism.  Wc  are 
then  confronted  with  another  question,  whether  we  are  dealing  with  a  variety 
of  diabetes  mellitus,  a  pentose  diabetes,  or  something  else.  If  we  are  dealing 
with  a  variety  of  diabetes  mellitus,  the  combustion  of  carbohydrates  must  be 
diminished,  as  in  the  case  of  diabetes.  Such  a  connection  must  be  thought  of, 
all  the  more  so  as  Ruff  has  produced  pentose  from  derivatives  of  grape  sugar 
by  oxidation  with  potassium  permanganate  and  hydrogen  peroxid,  and  it  is 
possible  that  the  human  organism  may  also  carry  on  this  process  of  oxidation. 
Further,  as  it  is  known  that  the  pentose  which  occurs  in  nature  and  enters  the 
body  with  the  food,  such  as  tlie  1-arabinose  and  1-xvloso,  undergoes  only  partial 
combustion  even  in  the  healthy,  it  is  not  unnatural  to  explain  pentosuria  by 
conceiving  that  the  patient,  from  the  forms  of  sugar  with  six  carbon  atoms, 
forms  pentose.  This  he  incompletely  oxirlizos.  and  hence  excretes  a  portion 
of  it.  If  this  view  were  correct,  with  the  withdrawal  of  starch  from  the  food 
pentosuria  should  disappear  or  at  least  lessen,  and,  on  the  other  hand,  with 
the  profuse  administration  of  starch  or  grape  sugar  the  pentosuria  should 
increase. 

But  when  we  withdraw  carbohydrates  from  patients  who  excrete  pentose, 
it  is  always  observed  that  the  pentosuria  continues,  and  apparently  in  the  same 
degree  as  formerly,  while  the  administration  of  even  100  grams  of  grape  sugar 
after  a  strict  diet  free  from  sugar  does  not  lead  to  a  decided  increase  of  the 


PENTOSURIA  265 

pentosuria.  From  these  results  it  is  obvious  that  pentose  in  the  animal  organ- 
ism is  not  formed  by  the  oxidation  of  hexose,  i.  e.,  the  varieties  of  sugar  with 
six  atoms  of  carbon  or  their  multiples. 

This  to  some  extent  also  answers  the  question  whether  pentosuria  is  a 
variety  of  diabetes  mellitus.  The  latter  disease  is  characterized  by  the  fact 
that  the  power  to  burn  starches  and  he.xoses  is  diminished.  That  this  is  not 
true  of  pentosuria,  at  least  not  of  all  cases  of  pentosuria,  was  shown  by  Bial 
and  myself,  for  the  administration  at  once  of  100  grams  of  grape  sugar  caused 
no  glycosuria.  The  combustion  of  d-galactose  in  our  case  of  pentosuria  was 
also  entirely  normal.  It  follows  from  this  that  the  patient  witb  pentosuria 
ha-  no  greater  tendency  to  alimentary  glycosuria  than  the  healthy;  hence  if 
we  look  upon  alimentary  glycosuria  as  a  proof  of  the  existence  of  diabetes 
mellitus,  the  urine  of  the  pentosuric  is  in  this  respect  also  entirely  negative. 
There  is  good  ground  for  the  supposition  that  pentosuria  is  a  pentose  diabetes, 
in  which  metabolism  for  sugar  with  six  atoms  of  carbon  is  normal,  while  //"' 
property  of  combustion  for  pentose  is  diminished  <>r  has  entirely  ceased.  With 
food  in  the  form  of  grain  and  fruit,  and  in  beer  and  tea  we  ingest  a  certain 
ammmt  of  pentosans;  it  is  quite  possible  that  pentosans  are  changed  into 
pentose  in  tip'  stomach  by  the  action  of  hydrochloric  acid;  but  the  organism 
is  incapable  of  oxidizing  them  and  tltey  are  therefore  excreted.  Tin-  hypoth- 
18  accepted  by  N'aunyn  and  Lüthje,  and  by  others.  Can  this  view  be 
possible? 

The  pento-e  which  we  ingest  with  our  fond  is  the  dextro-rotary  1-arabinose, 
while,  a-  we  know  from  tin'  investigations  of  Carl  Neuberg,  inactive  arabinose 
also  occurs  in  the  urine.  Since  inactive  arabinose,  a-  the  researches  of  Emil 
Fischer  have  shown,  can  only  occur  by  the  combination  of  d-arabinose  and 
l-arabinose,  the  organism  must,  in  addition  to  L-arabinose,  also  furnish  d-arabi- 
UO  e  :   SO  that  i-arabinose  may  be  formed. 

The  question  whether  the  organism  contain-  pentose  group-  ha-  been  dis- 
cussed for  a  longtime.  A-  i-  well  known.  Ilammar-ten  found  in  the  nucleo- 
proteid  of  the  pancreas  a  reducing  substance  which  he  assumed  to  be  pen! 
B.  Salkowski  has  produced  phenylosazone,  ami.  upon  the  basis  of  an  analysis 
of  the  same,  baa  determined  with  certainty  that  the  reducing  substance  is  pen- 
tose. <  >n  account  of  the  abundant  furfuro]  formation  which  is  said  to  be  char- 
acteristic of  pentose,  and  which  upon  decomposition  was  shown  to  be  present 
in  the  Qucleo-proteids  from  various  animal  organs,  and  on  account  of  the 
production  of  phenylosazones  at  the  melting  point  of  pentosazone,  157°  to 
L60  C,  I  have  maintained  that  all  animal  nucleins  contain  "  pentose  group, 
and  '.'■"/  Ihr  pentose  group  i-  characteristic  of  nucleins  just  a-  i-  the  group  of 
xanthin  bases,  for  I  found  no  proteids  which  contain  pentose  except  Qucleins. 
I  have  al-o  held  llml  when  <ni  albumin  body  gives  the  phlorogtucin  test  for 
pentose  we  are  justified  in  declaring  it  I"  contain  umhin.    This  view  at  the 

time  appeared  0,  he  decidedly  opposed  to  the  prevailing  opinion.  A.  Ko8se1 
and  Neumann  had.  \u<<  \>-.w-  previously,  found  no  pentose  group  in  nucleinic 
acid  of  the  thymus  gland.  The  former  denied  absolutely  the  presence  of  a 
carbohydrate  group  in  the  spermatic  nucleinic  acid.  Noll,  the  pupil  of  A. 
Cossel.  forbore  entering  into  this  discussion,     lie  believes  that  we  must  dis- 


266  PENTOSURIA 

criminate  sharply  two  reducing  carbohydrates.  One  is  loosely  combined  with 
the  nucleins,  and  in  the  formation  of  nucleinic  acid  separates  from  nuclein; 
the  second,  a  firmly  combined  atomic  group  with  a  molecule  of  nucleinic  acid, 
causes  the  production  of  levulinic  acid  and  formic  acid,  the  latter  of  which 
does  not  form  a  reducing  carbohydrate.  In  view  of  this,  Kossel's  adherents 
admitted  the  presence  of  a  reducing  carbohydrate  in  animal  nuclein,  but 
refrained  from  any  expression  regarding  the  nature  of  the  reducing  substance. 
Later,  Friedrich  Müller  questioned  the  opinion,  then  prevalent,  that  pentose 
was  the  sugar  of  the  vegetable  kingdom  and  did  not  occur  in  the  animal  king- 
dom. He  believed  there  was  often  a  confusion  of  pentose  with  glycuronic 
acid,  a  confusion  which  was  by  no  means  impossible  on  account  of  the  test 
then  in  vogue.  This  diversity  of  views  led  Bergell  and  myself  to  make  further 
researches  in  regard  to  pentosuria.  From  a  urine  supposed  to  contain  pento.se, 
he  and  I  obtained  a  barium  combination  of  the  questionable  sugar,  the  analysis 
of  which  showed  we  were,  in  fact,  dealing  with  pentose.  By  this  means,  the 
presence  of  pentose  in  the  urine  of  animals  was  further  confirmed  by  Jastro- 
witz  and  Salkowski,  and  the  production  by  Carl  Neuberg  of  pure  r-arabinose 
from  so-called  pentose  urine  furnished  proof  incontestable  in  every  respect. 
Furthermore,  Wohlgemuth,  who  at  my  suggestion  examined  the  nucleo-proteid 
of  the  liver,  produced  from  this  a  chemically  pure  phenylosazone  which  by 
analysis  proved  to  be  phenylpentosazone.  The  presence  of  pentose  in  animal 
organs  was  later  confirmed  by  other  competent  observers.  Tims  Xcumann, 
the  former  co-worker  of  Kossel,  found  that,  with  an  improved  teclmic.  nucleinic 
acid  obtained  from  the  thymus  gland  gave  a  decided  pentose  reaction.  The 
labors  of  Bang,  Jacob,  and  Bergell,  Friedenthal,  Umber,  Grund  and  others, 
proved  the  correctness  of  the  theory  first  suggested  by  me  that  not  only  all 
vegetables  but  also  all  animal  nucleo-proteids  contained  carbohydrates  belong- 
ing to  the  pentose  group. 

The  question  now  arises,  How  was  it  possible  that  these  groups  were  so  long 
overlooked  in  the  nucleins  by  prominent  investigators,  and  that  my  earlier 
results  were  so  long  unconfirmed?  This  must  be  ascribed  to  the  fact  that  in 
the  nucleo-proteid  of  the  thymus,  as  Umber  and  I  determined  in  the  pancreas 
proteid,  the  pentose  group  is  very  loosely  combined.  To  obtain  the  nucleo- 
proteid  of  the  thymus  a  solution  of  the  same  in  an  alkali  and  precipitation  with 
acetic  acid  are  sufficient  to  separate  the  greater  portion  of  the  pentose  and 
to  obtain  a  phosphorus-containing  albumin  body  that  no  longer  shows  pentose 
but  still  contains  some  xanthin  base-.  And  for  the  nucleo-proteid  of  the  pan- 
creas Umber  has  shown  that  the  pentose  group  is  one  of  the  first  products  of 
pepsin  digestion  which  enters  solution.  This  view  might  very  readily  coincide 
with  that  of  Kossel's  adherents  who  believe  that  the  reducing  carbohydrate 
is  very  loosely  attached  to  the  nucleo-proteid,  for  on  the  solution  of  thynrns- 
nuclein  in  alkali  a  phosphorus-containing  albumin  body  which  still  contains 
xanthin  liases,  i.  e.,  a  nuclein,  is  retained.  I  believe,  therefore,  that  such  a 
body  free  from  pentose  should,  at  most,  be  designated  an  atypical  nuclein. 

That  the  pentose  group  is  but  loosely  combined  with  the  nucleins  is  cer- 
tainly not  true  of  the  pancreas  nuclein,  for  Bang  has  obtained  pentose  from 
its  nucleinic  acid. 


PENTOSURIA  267 

According  to  recent  investigations  of  Xeumann,  pentose  is  present  in  the 
nucleinic  acid  of  the  thymus;  hence  it  follows  that  the  pentose  group  is  an 
integral  constituent  of  at  least  some  of  the  nucleinic  "rids,  if  not  of  all. 

Of  the  pentoses  which  occur  in  animal  nucleins,  that  of  the  pancreas  has 
been  most  minutely  investigated.  Bang  supposed  it  to  be  dextro-rotary,  and 
Neuberg  has  lately  arrived  at  the  surprising  conclusion  that  the  pancreatic 
pentose  is  l-xylose.  This  latter  theory  is  of  great  importance  as  bearing  on 
the  origin  of  pentose  in  chronic  pentosuria.  For,  if  on  other  ground-  we  were 
inclined  to  believe  that  the  pentose  of  urine  originates  from  the  pancreatic 
nuclein  such  an  opinion  would  by  this  result  be  proven  to  be  erroneous.  It  is 
impossible  to  understand  how  xylose  could  be  changed  into  arabinose.  It  i- 
true  that  we  have  only  proven  for  pancreatic  nuclein  that  its  pentose  is  l-xyl 
the  other  nucleins  have  not  been  investigated  in  this  respect. 

The  researches  in  metabolism  by  Bial  and  myself  have  also  made  it  appear 
unlikely  that  pentoses  are  formed  in  the  pentosurie  patient  by  an  imperfect 
nuclein  decomposition,  since  the  metabolism  of  the  pentosurie  shows  no  such 
increased  destruction  of  nucleins.  Neither  the  excretion  of  uric  acid  nor  the 
excretion  of  phosphoric  acid  is  increased  in  pentosuria.  It  also  appears  to  be 
impossible  that  the  inactive  arabinose  in  pentosuria  originate-  from  other 
nucleins,  and  not  alone  from  the  pancreas  nucleins,  and  we  must  search  else- 
where for  an  explanation  of  the  origin  of  pentose. 

Carl  Neuberg  ha-  giver  us  important  and  interesting  conclusions  in  this 
field.  Hedemonstrated  that  the  l-xylose  which  i-  found  in  pancreatic  nuclein 
originate-  from  grape  sugar;  now  we  have  assumed  for  a  long  time  that  glu- 
cose i-  partly  oxidized  from  glycuronic  acid.  If  we  consider  glycuronic  acid 
as  pentose  carbonic  acid,  C5H1005C02,  it  need  only  is\\f  oil'  ii-  carbo-s 
group  to  produce  dextro-rotary  l-xylose.  This  the  organism  requires  for  the 
construction  of  nuclein-.  On  Ihr  other  hand,  in  his  opinion,  the  r-arabinose, 
the  urinary  sugar  of  pentosuria,  originates  in  a  very  different  manner. 

As  i-  well  known,  milk  sugar  i-  -|>lit  up  in  the  intestine  into  dextrose  and 
galactose;  a  portion  of  the  galactose  is  certainly  utilized  for  glycogen  pro- 
duction. Another  portion  enter-  into  cerebrin,  for  Thierfelder  was  able  to 
demonstrate  the  presence  in  cerebrin  of  galactose.  The  galactose  contained 
in  cerebrin,  however,  i-  dextro-rotary,  like  the  galactose  contained  in  food. 
Bui  it  i-  very  easy  to  change  this  d-galactose  to  it-  inactive  form,  and  then 
from  the  inactive  galactose  inactive  arabinose  may  readily  be  produced  by 
oxidation.  Carl  Neuberg  is  therefore  of  the  (>/>ini<>n  Unit  inactive  arabinose 
originates  [nun  derivatives  of  <iitl<i<t<isc.  How  far  this  view  is  correct  i-  still 
uncertain,  for  the  behavior  of  i-galaetöse  must  be  tested  in  the  organism  of 
a  pentosurie  patient.  The  behavior  of  the  ordinary  d-galactose  ha-  Keen  stud- 
ied by  Bial  and  myself,  hut  we  were  unable  to  determine  an  increase  of  pentose 
excretion. 

It  i-  evident  from  these  considerations  regarding  pentosuria  that  prior 
to  it-  discovery  by  I-'..  Salkowski  we  bad  but  slighl  understanding  of  the  Bugar 
metabolism  of  the  human  organism,  and  that  in  pentosuria  we  are  dealing  with 
an  anomaly  of  sugar  metabolism  which  must  he  assumed  to  he  an  independenl 
one.     It  has  nothing  in  common  with  diabetes,  and  is  also  del  to  be  regarded 


268  PENTOSURIA 

as  a  pentose  diabetes,  for  the  property  of  combustion  of  the  pentoses  of  the 
food  is  nowise  altered.  The  same  conditions  are  present  here  as  in  levulosuria, 
which  Eosin  and  Laband  have  lately  determined  represents  an  anomaly  in 
the  production  of  levulose,  not,  however,  dependent  upon  a  disturbance  of  its 
combustion.  I  do  not  believe  it  can  be  doubted  that  in  true  diabetes  we  shall 
ultimately  reach  the  point  of  separating  a  group  of  cases  in  which  the  forma- 
tion of  grape  sugar  in  the  organism  is  disturbed :  while  there  is  no  anomaly 
of  combustion.  I  mean  the  cases  with  slight  excretion  of  sugar  ( 1  per  cent,  or 
less)  and  this  almost  entirely  independent  of  the  carbohydrate  constituents  of 
the  food.  Perhaps,  also,  in  many  severe  cases  such  a  disturbance  in  the  syn- 
thesis of  sugar  may  be  found. 

Pentosuria  is  therefore  an  independent  disturbance  of  metabolism,  which 
is  characterized  by  the  fact  that  in  this  condition  an  inactive  sugar  has 
been  found  in  nature  for  the  first  time.  Thereby  the  law  that  the  animal 
organism  and  plants  can  produce  only  active  varieties  of  sugar  has  been 
proven  erroneous.  A  second  law,  which  for  a  long  time  was  considered 
incontestable,  namely,  that  the  pentoses  are  the  sugar  of  the  vegetable  king- 
dom only,  and  do  not  occur  at  all  in  the  animal  kingdom,  has  also  been 
nullified. 

We  must  separate  true  chronic  pentosuria  from  alimentary  pentosuria. 
A  large  number  of  individuals  do  not  possess  the  property  of  oxidizing  large 
amounts  of  pentosan  introduced  with  the  food,  but  excrete  a  portion  of  these 
pentosans  as  pentose.  This  is  alimentary  pentosuria.  The  amount  of  pentose 
excreted  is  about  0.2  to  0.5  per  cent.  This  pentose  always  arises  from  the 
pentosans  which  are  taken  up  with  the  food,  for  the  most  part  in  the  dextro- 
rotary  1-arabinose  contained  in  fruits.  This  phenomenon  we  generally  see 
in  the  summer  when  fruit  is  freely  eaten  (cherries,  strawberries,  whortleber- 
ries, plums). 

This  alimentary  'pentosuria  has  nothing  in  common  with  chronic  pento- 
suria, in  which  arabinose  also  occurs;  here  not  the  dextro-rotary  but  the  inac- 
tive appears  in  the  urine.  We  now  find,  however,  that  besides  chronic  pen- 
tosuria the  alimentary  type  may  also  exist,  and  I  am  in  possession  of  record  3 
of  cases  in  which  both  the  inactive  arabinose  and  the  dextro-rotary  appear  in 
the  urine.  The  proof  of  this  has  been  deduced  as  follows:  first,  the  urine 
without  fermenting  was  dextro-rotary;  secondly,  only  pentosazone  could  be 
produced  from  it ;  and  thirdly,  according  to  Neuberg,  a  solution  of  the  osazone 
in  pyridin  alcohol  proved  dextro-rotary. 

True  chronic  pentosuria,  as  we  have  seen,  is  characterized  by  the  fact  that, 
independently  of  food,  inactive  arabinose  is  excreted  continuously.  The 
amount  of  inactive  arabinose  varies  in  this  condition  between  0.3  and  1  per 
cent,  by  Knapp's  method  of  titration. 

We  find,  however,  cases  also  of  chronic  diabetes  that  are  complicated  by 
pentosuria,  i.  e.,  showing  a  slight  excretion  of  pentose.  To  this  group  belong 
a  number  of  diabetics  in  whose  urine  very  small  amounts  of  pentose  have  been 
demonstrated,  as  shown  by  Kiilz  and  Vogel.  In  these  cases  the  pentose  has 
not  the  slightest  clinical  importance  so  far  as  can  be  determined  at  this  time. 
It  occurs  in  such  minute  traces  that  its  presence  cannot  be  detected  by  our 


PENTOSURIA  269 

common  tests,  ami  the  utilization  of  several  liters  of  urine  is  necessary  to  find 
the  substance  at  all.  We  have  no  knowledge  as  u>  which  pentose  appears  in 
tin-  urine  in  diabetes  (whether  pentose  of  the  food,  or  inactive  arabinose,  or 
pancroa-  pentose,  i.e..  l-xylose),  nor  do  we  know  whether  it  is  particularly  in 
the  severe  cases  of  diabetes  thai  pentose  is  excreted. 

To  quite  a  differenl  group  belong  those  cases  of  pentosuria  in  which,  besides 
pentose,  glycose  appears  transitorily  in  the  urine.  In  this  instance  the  gly- 
cosuria  may  have  an  accidental  cause  (morphin),  as  in  the  ease  of  Jastrowitz 
and  Salkowski  which  Led  to  the  discovery  of  pentosuria.  We  may,  however, 
encounter  the  combination  of  true  pentosuria  with  mild  diabetes.  I  have 
seen  such  a  case.  The  quantity  of  grape  sugar  amounted  to  0.6  to  1  per 
cent.,  the  amount  of  pentose  was  0.3  to  0.5  per  cent.  As  the  urine  was 
senl  to  me  for  investigation  only  a  few  times.  I  can  say  nothing  further 
about  the  course  of  the  case.  Only  this  much  could  he  determined,  that 
the  pentose  found  in  the  urine  was  inactive,  therefore  probably  an  inactive 
arabinose. 

The  second  group  of  chronic  eases  of  pentosuria  includes  the  pure  . 
Mi  which  no  other  sugar  limn  pentose  is  found.  Up  1o  tin-  time  the  following 
cases  are  reported  in  literature:  first,  the  case  of  Jastrowitz  ami  I-'..  Salkowski 
in  which  the  glycosuria  disappeared  after  morphin  was  stopped,  while  the 
pentosuria  proved  chronic:  secondly,  the  two  cases  described  by  Salkowski  and 
myself.  The  fir-t  of  these  occurred  in  a  merchant,  thirty-six  years  of  age, 
and  always  healthy,  who  was  married  and  had  four  living  children.  The 
amount  of  pentose  he  excreted  varied  between  0.1  and  1  per  cent.,  with  an 
average  amount  <>f  mine  of  a  liter  to  a  liter  and  a  half  per  day.  This 
occurred  in  L895  in  the  practice  of  Dr.  L.  Peilchenfeld  who  -till  has  the 
patient  under  observation.  Up  to  this  time  the  pentosuria  has  never  been 
associated  with  any  Berious  symptoms.  Tin-  patient  repeatedly  suffered  from 
hydrocele,  ami  the  fluid  obtained  by  puncture  was  examined  by  me  ami  found 
to  contain  grape  sugar  hut  no  pentose.  The  urine  ha-  also  been  utilized  by 
('.   Neuberg  for  the  preparation  of  r-arabinose.     The  patient   was  decidedly 

thin. 

The  third  case  occurred  in  a  banker,  aged  sixty-five.  This  patient  (ac- 
cording to  the  report  of  |)r.  Iihiiiiriitli.il.  who  treated  him  for  over  twenty  years 
before  the  pentosuria  was  discovered)  is  said  to  have  repeatedly  had  reducing 
substances  in  hi-  urine,  hui  grape  sugar  was  never  found  until  L895,  when  the 
pentosuria  was  discovered.  Tin-  case  is  especially  interesting  a-,  in  the 
family  of  the  patient,  numerous  chronic  diseases  occur,  particularly  diab 
and  Qervous  diseases.  Up  to  two  years  before  death  (which  occurred  in  1900) 
the  urine  in  thi-  case  constantly  Bhowed  about  one  per  cent,  of  pentose.  For 
some  time  before  death  he  was  treated  by  another  physician;  his  death  was 
due  to  arteriosclerosis.  The  autopsy  showed  calcification  of  the  coronary 
arteries;  the  pathologist  told  me  that  nothing  of  special  interest  was  found 
in  the  pancreas,  hut  unfortunately  he  had  nol  hen  informed  of  the  exi-! 
of  pentosuria. 

The  fourth  and  fifth  eases  wen-  published  by  Dr.  Bial.  The  fourth  was 
that  of  a  merchant    from   Warsaw,  aged  thirty-e\en.  who  suffered    from  mild 


270  PENTOSURIA 

gastric  and  intestinal  symptoms  and  supposed  himself  to  be  a  diabetic.  Small 
amounts  of  sugar  had  been  frequently  found  in  his  urine,  and  a  suitable  diet 
had  been  advised.  The  report  from  a  Warsaw  chemical  laboratory  shows 
slight  quantities  of  sugar  found  by  Trommer's  test  and  a  positive  reaction  to 
Phenylhydrazin.  This  patient  was  also  conspicuously  thin.  Bial  determined 
that  pentose  was  present  in  the  urine  in  July,  1898,  as  well  as  constantly  for 
twenty  days  in  July,  1899,  but  no  grape  sugar  could  be  found. 

Case  V  (Bial).  A  druggist,  twenty-eight  years  old,  perfectly  well.  The 
amount  of  pentose  in  Case  IV  amounted  to  0.3  per  cent.,  in  Case  V,  0.35  per 
cent. 

Case  VI.  Eeported  by  Dr.  Fritz  Meyer.  A  merchant,  aged  thirty-nine, 
never  previously  ill,  was  rejected  by  a  life  insurance  company  six  years  ago, 
and  before  the  discovery  of  pentosuria,  on  account  of  diabetes.  He  was  treated 
in  Carlsbad,  was  on  a  strict  diet,  and  was  declared  to  be  cured  as  the  examina- 
tion of  his  urine  by  the  polariscope  showed  optical  inactivity.  Five  years  ago 
he  married,  and  is  now  the  father  of  a  healthy  child.  His  health,  with  the 
exception  of  a  mild  attack  of  perityphlitis,  has  always  been  good.  In  April, 
1900,  symptoms  appeared  which  gave  rise  to  the  suspicion  of  a  constitutional 
disease;  his  weight  is  said  to  have  decreased  decidedly;  it  amounted  to  150 
pounds.  He  complained  of  headache,  lumbar  pains,  lassitude,  vertigo,  and 
severe  neuralgia,  particularly  in  the  region  of  the  sciatics.  The  urine 
amounted  to  1,800  c.c. ;  it  was  clear,  contained  no  formed  elements,  and  was 
without  albumin.  The  urine  reacted  positively  to  Trommer's  and  Moore's 
tests ;  being  optically  inactive  it  was  examined  for  pentose,  and  pentosuria  was 
determined. 

In  the  seventh  case,  the  patient  was  an  American  lady,  who  had  been  several 
times  under  treatment  in  Carlsbad  on  account  of  supposed  diabetes.  Her  case 
was  always  considered  to  be  a  severe  one,  for,  in  spite  of  the  strictest  diet,  it 
was  never  possible  to  render  the  urine  aglyeosuric.  In  this  case  quite  a 
decided  amount  of  pentose  was  found,  over  1  per  cent.,  but  not  the  slightest 
trace  of  grape  sugar. 

The  eighth  case  (Dr.  Brat)  occurred  in  a  lady,  aged  sixty-two,  who  for 
several  years  was  under  professional  treatment  on  account  of  a  presumably 
mild  diabetes.  She  had  a  slight  degree  of  fatty  heart,  otherwise,  however, 
she  was  quite  well.  This  lady  has  been  under  my  observation  for  more  than 
a  year,  and  in  this  entire  time  has  never  excreted  grape  sugar.  In  her  case, 
however,  the  urine  was  somewhat  dextro-rotary,  0.2  per  cent.,  and  I  believe  it 
therefore  not  unlikely  that,  besides  inactive  pentose,  a  dextro-rotary  pentose 
was  present  in  slight  degree. 

Case  IX.  The  brother  of  the  patient  just  described  (Case  VIII),  aged 
about  fifty,  perfectly  well.  His  urine  showed  about  75  per  cent,  of  pentose. 
According  to  analyses  made  by  several  chemists  since  1892,  0.2  to  2  per  cent,  of 
sugar  was  determined.  One  found  only  a  reducing  property  in  the  urine  but 
no  sugar.  There  is  no  question  in  my  mind  that  the  gentleman  was  not  dia- 
betic, for  a  breakfast  containing  large  amounts  of  sugar  gave  no  results.  The 
case  is  otherwise  of  no  clinical  interest;  the  other  brothers  and  sisters  present 
neither  diabetes  nor  pentosuria. 


PENTOSURIA  271 

Additional  cases  of  pentosuria  have  been  described  by  Colombini  in  mor- 
phin habitues;  by  Caporelli  in  xanthoma,  others  by  Reale  and  Romme,  and  a 
case  of  alimentary  pentosuria  with  glycosuria  by  Barszewsky. 

It  is  not  remarkable  that  so  many  cases  of  pentosuria  have  been  confounded 
with  diabetes,  for  the  qualitative  tests  are  the  same.  The  important  ques- 
tion is,  and  remains:  Has  pentosuria  anything  in  common  with  diabetes?  Have 
pentosurics  on  account  of  their  pentosuria  a  special  liability  to  become  diabet- 
ics? On  account  of  what  has  been  above  stated  these  questions  must  be 
answered  negatively. 

Pentosuria  is  a  disturbance  of  metabolism  which  is  connected  perhaps  with 
cerebrin  metabolism,  perhaps  with  the  formation  of  galactose.  Negatively  the 
principal  point  is  that  there  is  no  evidence  of  insufficiency  in  the  utilization  of 
the  carbohydrates  consumed  with  the  food. 

Another  question  now  arises:  What  is  the  prognosis  of  pentosuria?  It  is 
unwise  to  express  a  dogmatic  opinion  on  this  point  since  we  have  known 
the  disease  for  only  a  decade.  Notwithstanding  this,  it  may  be  said  that  the 
prognosis  is  probably  much  more  favorable  than  in  mild  diabetes,  for  the  pen- 
tosuric  utilize-,  fully  the  starches  and  other  carbohydrates  which  are  adminis- 
tered with  the  food,  and  the  amount"  of  pentose  which  he  forms  and  excretes 
is  small,  at  most  from  15  to  20  grams  per  day.  This,  therefore,  represents 
no  more  serious  prognosis  than  the  mildesi  cases  of  diabetes.  Upon  the  other 
hand  it  musl  not  be  forgotten  that  sugar  is  circulating  in  the  blood.  That 
this  is  true  is  obvious  from  the  investigations  conducted  by  Bial  and  myself, 
as  we  have  proven  the  presence  of  arabinose  in  the  blood.  I'.ut  the  presence 
of  a  large  quantity  of  sugar  in  the  blood  lead-  to  arteriosclerosis,  and  may 
give  rise  to  other  changes. 

Whether  the  pentosuric  is  more  susceptible  to  infections  than  a  healthy 
person,  as  is  the  case  with  diabetics,  is  very  difficuH  to  say.  for  up  to  the  pres- 
eni  time  the  data  are  very  scanty.  CTpon  the  whole,  and  in  the  majority  of 
cases,  the  prognosis  of  pentosuria  can  certainly  not  be  termed  very  serious. 

Regarding  therapy,  such  treat m  as  we  employ  in  diabetes  i-  oul  of  place 

in  pentosuria,  as  is  obvious  from  all  that  has  been  stated.  In  general  only 
tin-  much  is  to  be  said:  (1)  A  pure  meal  diet,  according  to  the  experience 
of   Fritz  Meyer  and   myself,  is  not   well  borne  by  pentosurics,  for  neuralgic 

symptom-,  if  present,  are  increased.  (2)  A  milk  diet  is  found  to  be  particu- 
larly advantageous. 

In  conclusion,  a  word  regarding  the  frequency  of  the  disease.  Although 
it  may  be  assumed  from  the.  a-  yet,  Bcanl  publications  that  pentosuria  is  a 
rare  affection,  I  cannot  admit  that  it  i-  to  he  regarded  a-  a  curiosity  like 
maltosuria.  Such  a  comparison  i-  incorrect,  for  pentosuria,  in  the  iir-t  place, 
gives  ii-  a  very  interesting  insight  into  disturbances  of  metabolism;  and 
ondly,  it  cannot  be  considered  immaterial  that  a  person,  a-  in  almost  all  id'  the 
cases  that  have  been  cited  here,  should  be  supposed  for  years  to  be  ;i  diabetic, 
and  subjected  t<>  dietetic  and  mineral  Bpring  treatment  which  is  absolutely 
out  of  place,  hi  life  insurance  the  decision  i-  of  the  greatest  importance.  The 
pentosurics  mn-t  at  least  be  admitted  to  have  a-  favorable  a  prognosis  as  the 
mild  cases  of  diabetes. 


272  PENTOSURIA 

If  it  be  further  remembered  that  nine  cases  have  been  detected  in  Sal- 
kowski's  laboratory  and  in  the  First  Medical  Clinic  of  Berlin,  the  affection 
cannot  be  so  rare  as  many  believe.  Hence  a  knowledge  of  this  disturbance  and 
of  the  means  to  its  diagnosis  is  an  absolute  necessity  for  every  physician. 

Briefly  the  most  important  diagnostic  factors  are  as  follows:  Positive 
orcin  test  with  negative  fermentation  test  proves  pure  pentosuria;  positive 
orcin  test  and  positive  fermentation  test  denote  pentosuria  und  glycosuria. 

A  turning  to  the  right  of  the  polariscope  does  not  prove  the  non-existence 
of  pentosuria,  for  dextro-rotary  pentose  also  occurs  in  the  urine. 


DISEASES    OF    THE    BLOOD 


L9 


BLOOD    AND     BLOOD     EXAMINATION 
By   A.    LAZARUS,    Charlottenburg    (Berlin) 

Tin-:  examination  of  the  blood,  in  comparison  with  other  clinical  investi- 
gation.-, has  .very  Blowly  forced  its  way  into  practice.  While  the  conscientious 
physician  rarely  fails  to  make  an  examination  of  the  urine  or  of  the  sputum 
in  cases  in  which  it  seems  necessary  or  at  all  useful,  examinations  of  the  blood, 
even  the  simplest,  have  up  to  the  present  been  resorted  to  by  a  very  small 
number  of  practitioners. 

The  object  of  this  article  is  to  call  attention  to  the  necessity  of  clinical 
blood  investigation,  and  to  describe  the  simplest  methods.  It  will  then  become 
a  matter  of  routine  to  examine  the  blood  no  less  frequently  than  the  various 
other  secretions,  excretions,  or  inflammatory  products. 

Of  course,  the  importance  of  the  results  of  blood  investigation  in  different 
diseases  of  the  blood  is  not  always  equally  great.  In  the  cases  in  which  a  dis- 
ease of  the  blood  or  of  the  blood-producing  organs  comes  into  question,  an 
examination  of  the  blood  is  more  important  than  any  other  clinical  research, 
and  often  this  alone  will  guide  US  to  a  definite  opinion.  This  is  true  of  the 
various  forms  of  anemia,  of  leukocytosis  and  Leukemia,  of  many  diseases  of  the 
bone-marrow,  and  in  certain  parasitic  diseases  of  the  blood.  [There  can 
hardly  be  -aid  to  be  "many  diseases  of  the  bone-marrow"  recognized  to-day, 
and  the  blood  has  never  yet  helped  much  to  advance  our  knowledge  in  thi- 
direction. 

Parasitic  diseases  of  the  intestine  and  other  internal  organs  should  be  men- 
tioned here  among  those  in  which  blood  examination  is  of  great  diagnostic 
value. —  Ed.  I 

The  number  of  cases  is,  however,  disproportionately  greater  in  which  an 
examination  of  the  blood,  although  actively  complementing  other  method-,  is 
alone  not  decisive.  It  may  be  of  value  in  the  differential  diagnosis  between 
various  acute  infection-  diseases;  it  may  make  clear  the  nature  of  many  cases 
of  poisoning;  in  the  prognosis  of  many  bacteria]  diseases  we  may  under  Borne 
circumstances  find  points  of  Bupporl  in  the  condition  of  the  blood  ;  the  prophy- 
laxis and  therapy  of  malaria,  according  to  Roberl  Kodi*-  investigations,  can 
only  be  made  certain  by  regular  examination-  of  the  blood,  and  to  these  many 
other  examples  mighl  be  added  [e.g.,  trichiniasis,  filariasis,  uncinariasis, 
trypanosomiasis. —  Ki>.  |. 

That  the  history  under  Bome  circumstances  may  become  enriched  by  an 
examination  of  the  blood  is  obvious  if  we  remember  that  after  recovery  from 


276  BLOOD  AND   BLOOD  EXAMINATION 

certain  infectious  diseases  protective  bodies  may  be  demonstrated  in  the  blood 
serum. 

After  these  brief  indications  it  will  be  seen  that  we  have  quite  a  large  field 
of  activity,  even  if  Ave  limit  ourselves  to  such  an  investigation  of  the  blood 
as  is  of  immediate  clinical  importance.  It  is  impossible,  however,  to  omit  a 
brief  explanation  of  the  normal  physiology  and  anatomy  of  the  blood,  as  this 
enables  us  to  measure  the  degree  of  pathological  change  liable  to  occur. 

We  must  first  decide  upon  the  best  method  of  obtaining  the  amount  of 
blood  necessary  for  investigation.  Of  course  for  clinical  purposes  only  those 
methods  of  examination  are  valuable  which  need  no  more  than  one  or  two 
c.c,  or — if  there  be  a  necessity  for  frequent  repetition — a  few  drops  of  blood. 
Consequently,  many  clinical  methods,  compared  with  strict  physiological 
processes,  suffer  more  or  less  in  reliability.  This  fact  has  lately  given  rise  to 
an  endeavor  to  modify  certain  physiological  methods  which  hitherto  have 
necessitated  large  quantities  of  blood.  The  results  have,  in  the  main,  been 
rather  unsatisfactory.  This  is  true,  for  example,  of  the  "  clinical "  estima- 
tion of  the  alkalinity  of  the  blood,  and  of  the  iron  and  phosphorus  in  the  blood. 
If  large  quantities  of  blood  cannot  be  obtained,  it  is  better  to  refrain  entirely 
from  such  estimations  than,  by  an  appearance  of  exactness,  to  produce  figures 
of  questionable  value. 

Fortunately,  however,  for  many  important  clinical  investigations,  only  a 
few  drops  of  blood  are  necessary,  and  these  are  best  obtained  under  aseptic 
precautions  by  a  simple  prick  of  the  finger,  of  the  toe,  or  of  the  lobe  of  the  ear. 
[In  America  the  finger  is  rarely  used,  as  the  pain  of  puncture  is  much  greater 
than  in  the  ear.  An  ordinary  glover's  needle  (bayonet-pointed)  is  convenient, 
cheap  and  efficient.  A  sewing  needle  can  be  used  but  does  not  answer  nearly 
as  well. — Ed.]  By  friction  or  by  active  muscular  movement  these  portions  of 
the  body  may  previously  be  made  somewhat  hyperemic.  In  general  the  choice 
of  the  place  is  immaterial :  for  smear  preparations  the  finger  is  preferred. 
In  very  sensitive  patients,  provided  the  investigation  is  to  be  repeated  fre- 
quently, the  ear  is  chosen.  The  prick  is  made  with  half  of  a  steel  pen  or  with 
a  Soennecken's  lancet:  but  we  may  also  use  the  so-called  "pistol  knife"  in 
which  the  needle-shaped  knife  may  be  adjusted,  and.  by  pressure  of  the  spring, 
inserted  to  an  exact  depth. 

If  larger  quantities  of  blood,  i.  c.,  a  few  cubic  centimeters  or  more,  are 
necessary  it  is  advisable,  provided  there  is  no  contra-indication,  to  obtain  the 
material  by  wet  cups ;  in  which  proceeding  it  must  of  course  be  remembered 
that  blood  thus  obtained  is  more  or  less  admixed  with  lymph.  Finally  punc- 
ture of  a  dilated  vein  of  the  arm  by  the  aid  of  a  Pravaz  syringe,  which  is  very 
readily  performed,  or  an  ordinary  venesection  may  be  resorted  to. 

The  withdrawal  of  blood,  if  performed  aseptically,  is  entirely  without  dan- 
ger and.  as  a  rule,  does  not  disturb  the  patient  in  the  least.  We  should  never 
forget,  before  proceeding,  to  assure  ourselves  that  we  are  not  dealing  with  a 
hemophilic.  In  such  persons,  even  with  a  simple  puncture  of  the  finger,  there 
may  be  great  difficulty  in  stopping  the  flow  of  blood.  [In  such  cases  a  mere 
touch  of  the  needle  point  to  the  skin  will  give  us  all  the  blood  needed  without 
producing  any  troublesome  hemorrhage. — Ed.] 


HEMOGLOBIN  277 


I.    HEMOGLOBIN 


The  exuding  drop  of  blood  shows  oven  to  the  naked  eye  a  number  of  prop- 
erties. The  redder  it  is,  the  richer  it  is  in  oxyhemoglobin;  the  darker,  the 
greater  the  amount  of  reduced  hemoglobin.  Accordingly,  it  is  at  once  re 
oized  from  these  properties  whether  the  blood  originates  from  the  arterial  and 
capillary  vessels  or  from  the  venous  system.  In  carbonic  acid  poisoning  the 
color  of  the  blood  is  particularly  bright  and,  as  a  rule,  is  designated  as 
cherry- red. 

In  the  red  oxygen-containing  blood  differences  in  the  intensity  of  the  color- 
ing are  readily  determined,  bul  these  are  frequently  not  easy  of  recognition 
in  very  dark  venous  blood.  Such  differences  become  more  noticeable  if  the 
drop  of  blood  is  caught  and  spread  out  upon  white  linen  or  upon  white  blot- 
ting paper:  the  greater  or  lesser  staining  power  of  different  drops  of  blood  is 
very  well  demonstrated  in  this  simple  manner,  and,  with  some  practice,  from 
the  color  of  the  stain  a  conclusion  may  be  drawn  as  to  the  amount  or  hemo- 
globin in  the  blood.  Following  this  principle,  Tallqvist  has  described  a 
"hemoglobin  scale"  by  the  aid  of  which  gross  differences  in  the  amount  of 
hemoglobin  may  be  quite  accurately  estimated.  [The  Tallqvisl  scale  gives  ns 
not  ideal  accuracy  hut  all  the  accuracy  that  we  can  use  in  diagnosis,  prog] 
and  treatment,  [ts  errors  rarely  exceed  10  peT  cent.,  and  in  the  hands  of  the 
unskilled  other  and  more  "  accurate  "  instruments  often  -how  more  errors  than 
this.  The  cheapness  of  the  scale  and  the  ease  and  quickness  of  using  it  are 
also  important  recommendations. —  Ed.  j 

Accuracy  is  greater  with  apparatus  especially  constructed  for  the  estima- 
tion of  the  coloring  power  of  the  blood,  the  so-called  hemoglobinometer.  This 
apparatus  is  quite  properly  named  :  for,  in  the  main,  it  is  the  amount  of  hemo- 
globin contained  which  determines  the  coloring  property  of  the  blood;  the 
importance  of  a  few  other  coloring  substances  contained  in  the  blood  is  in 
comparison  quite  insignificant. 

For  clinical  purposes  a  large  number  of  blood  colorimeters  have  been  de- 
scribed; on  account  of  their  simplicity  Gpwers's  hemoglobinometer  and 
Flei8chl'8  hemometer  are  mosi   used,  and   will  now  be  described   (Dare  and 

Oliver). 

The  principle  of  the  Fleisch]  hemometer,  as  modified  by  Miescher,  is  the 
following:  By  the  aid  of  a  pipette  which  is  furnished  with  the  apparatus  (Fig.  9 
Mel.)  an  exactly  determined  amounl  of  Mood  is  dissolved  in  a  measured  quan- 
tity of  distilled  water;  the  color  of  this  solution  is  compared  with  that  of  a 
colored  glass  wedge  which,  by  its  gradually  increasing  thickness,  represents  a 
scale  of  blood  concentrations.     The  poini  in  the  wedge  is  now  searched   for 

which  is  just  a-  intensely  colored  a-  the  solution  of  blood  that   is  to  1 \am- 

ined,   and    the  number    i-   read    oil'    which    i-    found   at    this   point    of  the   glass 

wedge.     If.  for  example,  the  color  of  the  blood  solution  is  equal  l<»  that  <]■ 
nateil  a-  ', .".  in  the  glass  wedge,  it   means  that  the  examined  blood  contains 
oer  cent,  of  the  normal  amount  of  hemoglobin.     Besidi  stimation 

of  the  percentage  of  hemoglobin,  this  apparatus  also  make-  it   possibl 


278 


BLOOD  AND  BLOOD  EXAMINATION 


reckon  the  absolute  amount  of  hemoglobin  in  milligrams  in  1  c.mm.  of  blood. 
[It  is  essential  to  remember  that  percentage  readings  are  very  misleading  when 
applied  to  children,  since  their  normal  is  about  75  per  cent,  of  the  normal  of 
adult  men.  Women's  blood  contains  10-15  per  cent,  less  coloring  matter  than 
men's.  All  hemoglobin  instruments  should  be  graduated  in  milligrams  per 
c.mm.  of  blood  instead  of  in  percentages  of  a  supposed  "  normal." — Ed.]  The 
investigation  is  rather  laborious  because  it  can  only  be  carried  out  with  arti- 
ficial illumination.  The  apparatus  is  quite  expensive  on  account  of  the  diffi- 
culty in  manufacturing  the  glass  wedge.  Its  use,  however,  is  valuable,  for 
an  investigator  in  constant  practice  is  able  to  reduce  the  errors  to  5  per  cent, 
and  less. 

The  little  apparatus  of  Growers-  works  on  the  following  principle :  A  tube 
contains  a  standard  color  solution  which  possesses  the  tint  of  a  diluted  watery 


Fig.  9. — Hemometer.      (After  v.  Fleischl-Miescher.) 


hemoglobin  solution.  In  a  graduated  glass  tube  of  the  same  size  a  small  but 
accurately  determined  amount  of  blood  is  diluted  with  water  until  it  is  the 
same  color  as  the  color  in  the  test-tube;  naturally  this  occurs  the  sooner  the 
thinner  the  blood  is  at  the  beginning.  If,  for  example,  an  equalization  of 
color  is  reached  at  60,  this  indicates  that  the  blood  only  contains  60  per  cent, 
of  hemoglobin  in  comparison  to  normal  blood. 

This  test  is  quite  simple  and  it  may  be  completed  in  a  few  minutes  during 
the  office  hour;  the  apparatus  is  very  cheap.  With  a  well  made  instrument 
the  errors  may  be  reduced  to  from  10  to  5  per  cent.  I  must  call  attention  to 
the  fact  that  the  manufacture  of  this  apparatus  is  carried  on  by  some  quite 
unreliable  manufacturers,  so  that,  for  example,  test  solutions  are  furnished  in 


HEMOGLOBIN7 


279 


color  tints  such  as  thin  watery  blood  solutions  never  show.     Probably  because 

of  these  poor  instruments,  there  has  been  a  partial  opposition  to  the  use  of  the 

Gowers  apparatus. 

A  short  time  ago  Sahli  made  a  change  in  the  Gowers  hemoglobinometer, 

which  appears  to  have  added  greatly  to  the  value  of  the  apparatus.     For  this 

purpose  the  measured  quan- 
tity of  blood  is  first  placed 
in  a  slightly  diluted  hydro- 
chloric acid  solution  which 
produce-  a  dark  brown  so- 
lution   of    hvdrochlorate    of 


Pia.  10. — Hemometeb.    (After  Sahli.) 


Fig.  11. — Hemometeb,     (After  Sahli.) 


hematin.  This  mixture  La  then  diluted  with  water  until  it  corresponds  ex- 
actly in  eolor  to  a  tesl  solution  which  is  furnished  with  the  apparatus,  which 
also  consists  of  hydrochlorate  of  hematin  in  a  definite  dilution.  From  the 
amount  of  water  necessary  to  produce  this  correspondence  in  color,  we  may 
estimate  the  amount  of  hemoglobin  in  the  drop  of  blood  that  has  been 
tested.  In  its  mechanism  the  apparatus  is  much  superior  to  the  original, 
as  may  be  Been  in  the  two  illustrations  which  are  placed  side  by  side  (Figs. 
10  and  I  1  ). 

Among  otheT  instruments  (of  which  there  is  a  greal  number,  cadi  investi- 
gator having  his  favorite  one)  I  should  like  to  mention  one  of  the  Latest,  the 
practical  importance  of  which  upon  a  large  Bcale  must  -till  be  proven,  and  the 
use  of  which  is  Bomewhat  more  difficult  than  of  those  previously  depicted  :  t In- 
principle,  however,  is  interesting,  and  differs  greatly  from  thai  of  the  colorime- 
tric  ones  that  have  been  described  ;  for  this  reason  it  is  necessary  to  compare  Its 
results  with  those  obtained  by  the  aid  of  other  instruments.  I  refer  to  the 
hemophotograph  of  GaertneT  (see  Pigs.  L2  and  L3).  Gaertner  started  from 
the  observation  that  the  permeability  of  a  diluted  watery  blood  solution  for  the 
photographic  rays  of  sunlighi  was  in  inverse  proportion  to  its  hemoglobin  con- 
tent. For  this  reason  he  spreads  the  blood  solution  fco  1"'  examined  in  a  layer 
of  definite  and  uniform  thickness,  lays  photographic  paper  under  it.  and  per- 


280 


BLOOD  AND  BLOOD  EXAMINATION 


mits  the  sunlight  to  penetrate  this  for  a  definite  time.  The  degree  of  black- 
ening which  the  paper  shows  under  the  blood  layer  is  compared  with  a  stand- 
ard scale,  and  then  the  hemoglobin  is  read  from  a  table  which  has  been  obtained 
empirically. 

In  quite  a  series  of  investigations  I  have  compared 
the  results  obtained  with  the  apparatus  of  Gowers  and 
Gaertner  and  have  found  reasonable  uniformity. 


Fig.  12. — Hemophotograph.     (After  Gaertner.) 


Fig.  13. — Hemophotograph. 
(After  Gaertner.) 


When  by  the  aid  of  some  of  these  instruments  a  result  has  been  obtained, 
it  must  always  be  borne  in  mind  that  no  exact  test  has  been  made,  that,  on  the 
contrary,  all  sorts  of  errors  may  be  present.  Those  which  are  due  to  the 
imperfections  of  the  instrument  I  have  already  pointed  out;  and  we  must 
always  assume  5  to  10  per  cent,  of  errors  in  the  examination  of  a  definite  drop 
of  blood,  even  although  we  are  quite  expert  in  the  examination;  with  the 
novice  this  percentage  may  be  much  greater.  Unfortunately,  it  is  impos- 
sible by  the  use  of  more  exact  so-called  physiologic  methods  to  avoid  these 
errors  in  the  estimation  of  hemoglobin,  partly  because  the  methods  are  com- 
plicated, and  partly  because  they  require  too  large  amounts  of  blood,  and, 
therefore,  cannot  be  utilized  in  practice. 

To  these  errors,  which  are,  however,  due  to  the  methods  or  instruments, 
still  others  must  be  added  which  are  due  to  a  certain  changeability  in  the 
blood  itself.  It  is  well  known  that  the  most  varied  influences  may  change 
the  caliber  of  the  blood-vessels,  by  stimulating  the  vaso-dilators  or  the  vaso- 
constrictors; for  example,  light,  heat,  cold,  muscular  activity,  etc.  Accord- 
ing to  the  caliber  of  the  vessels — of  course  within  certain  narrow  limits — 
the  number  of  corpuscles  in  the  capillary  blood  will  vary,  and  with  this  the 
amount  of  hemoglobin,  the  specific  gravity,  the  total  solids  and  the  albumin 
contents  of  the  blood.  Moreover,  if  the  blood  to  be  examined  is  not  obtained 
by  puncture  or  incision  of  the  blood-vessel  directly,  but,  as  in  the  great  major- 
ity of  cases,  by  a  prick  in  the  finger  or  by  wet  cups,  the  unavoidable  admixture 


COUNTING  THE  BLOOD-CORPUSCLES  281 

of  tissue  lymph  to  the  blood  means  another  source  of  error,  although  in  itself 
not  a  great  one. 

In  spite  of  all  these  objections,  which  should  be  constantly  borne  in  mind, 
the  clinical  estimation  of  hemoglobin  is  of  great  value;  in  practice  it  is  un- 
questionably more  important  than  all  other  methods  of  blood  examination. 
The  decision  of  the  most  important  question,  whether  the  patient  be  anemic 
or  not,  can  only  be  made  positively  by  a  hemoglobin  test.  The  physician 
should  accustom  himself  to  look  upon  an  examination  of  a  patient  as  com- 
plete only  after  the  blood  has  been  examined  by  the  aid  of  a  hemoglobinometer ; 
then  a  surprisingly  large  number  of  persons  will  be  found  whose  blood  will 
show  quite  a  different  condition  from  what  might  have  been  expected  before 
the  examination  from  their  general  appearance.  My  estimation  is  rather  too 
low  than  too  high  when  T  say  that  fully  one-half  of  those  who  arc  pale,  who 
have  pale  mucous  membranes  and  cool  extremities,  and  for  this  reason  usually 
designate  themselves  as  "anemic''  show  a  perfectly  normal  amount  of  hemo- 
globin. Such  persons  do  not  suffer  from  an  abnormal  composition  of  the 
blood,  but  from  its  abnormal  distribution.  That  the  greatesl  differences  in 
regard  to  treatmenl  will  result  from  tins  in  individual  cases  certainly  requires 
no  further  demonstration.  I  shall  only  point  to  the  futility  of  many  a  treat- 
ment by  iron  :  due  to  the  fact  that  the  treatment  was  begun  without  any  indi- 
cation for  it,  i.  e.,  without  proof  of  a  diminution  in  the  amount  of  hemoglobin. 
A  careful  test  of  the  amounl  of  hemoglobin  in  the  blood  would  in  many  cases 
cause  11-  to  relinquish  the  iron  treatment  and  lead  to  the  use  of  other  cura- 
tive methods. 

In  conclusion  I  must  add  that  a  diminution  in  hemoglobin  may  occasion- 
ally be  discovered  where  the  external  appearances  by  no  mean-  indicate  anemia  ; 
of  course  a  correcl  estimate  of  the  degree  of  anemia  in  such  cases  musl  depend 
upon  a  te-t  of  the  hemoglobin. 

The  chief  value  of  the  clinical  investigation  of  hemoglobin  depends  upon 
the  fact  that  it  soon  informs  as  whether  and  to  what  degree  the  blood  may  be 
looked  upon  as  anemic;  from  this  we  can  determine  whether  to  investigate 
the  blood  for  other  change-  or  not. 

II.    COUNTING   THE    BLOOD-CORPUSCLES 

For  this  purpose  we  use  exclusively  the  Thoma-Zeiss  counting  apparatus 
(  Fig.  1  I).     This  consists  of  a  pipette  0  with  a  mixing  chamber  h\  in  which 

the  one  or  ten  per  cent,  blood  dilutions  are  made;  and  of  a  counting  chamber 
D  and  c  in  which  under  the  micro-cope  l<><>  divisions  may  be  recognized,  each 
containing  ,,,'„„  c.iiini.  In  counting  the  red  blood-corpuscles  the  following 
method  is  pursued  :  The  blood  js  sucked  up  to  a  definite  mark  in  the  capillary 
tube,  and  then  diluted  with  a  preserving  fluid.  We  use  exclusively  Hayem's 
solution,  the  composition  of  which  is  the  following: 

Mercuric  chlorid  (,."> 

Sodium  sulphate 5.0 

Sodium  chlorid    I.(t 

Aq.  desl 800.0 


282 


BLOOD  AND  BLOOD  EXAMINATION 


A  drop  of  the  diluted  solution  is  allowed  to  fall  upon  the  counting  cham- 
ber, the  cover-glass  is  placed  over  it,  and  this  is  permitted  to  sediment  for  a 
short  time.      [Tiirck's  emendation  of  this  step  in  technic  is  of  value.     Before 


(m 


0.100mm. 
1   ,.mm 


^\ 


C.  Zeiss 
Jena, 


Fig.  14. — Hemocytometer.     (After  Thoma.) 

blowing  out  a  drop  of  diluted  blood  upon  the  counting-disc,  he  puts  on  2 
corners  of  the  shelf  (  W,  Fig.  14),  that  is,  to  support  the  cover-glass,  a  minute 
drop  of  water.  The  diluted  blood  drop  is  then  adjusted  on  the  counting  disc 
and  as  rapidly  as  possible  the  cover-glass  is  let  down  and  pressed  firmly  into 

position  by  strong  pressure  with  the  thumbs. 
Newton's  rings  are  then  visible  at  once,  and  the 
cover-glass  is  sealed  firmly  in  position. — Ed.] 
After  which  (using  about  300  diameters  magnifi- 
cation) as  many  as  possible  of  the  squares  in  view 
should  be  counted.  If,  for  example,  we  have 
diluted  the  blood  1 :  100  and  then  count  in  32 
squares  (Fig.  15)  300  red  blood-corpuscles,  the 
following  calculation  is  made  (we  must  multiply 
with  100  to  compensate  for  the  blood  dilution)  : 

300X4000X100  .? 


Fig.  15.  —  The  Microscopic 
Picture  with  Blood-Cor- 
puscles.    (After  Landois.) 


32 


=  3 


This  is  the  number  of  red  blood-corpuscles  con- 
tained in  a  cm  it i. 

Any  one  in  constant  practice  with  this  instrument  possesses  an  exact  meas- 
uring apparatus  in  which  the  danger  of  error  is  very  slight;  naturally,  the 
aggregate  of  inaccuracies  is  less  when  more  squares  are  counted.  [Of  course 
the  amount  of  error  depends  on  the  number  of  squares  counted.  With  men 
properly  trained  no  constant  practice  is  needed.  My  own  practice  is  to  count 
100  squares.     The  error  is  then  negligible. — Ed.] 

It  must  be  noted  that,  particularly  in  extreme  anemia,  the  number  of 
blood-corpuscles  may  easily  be  reckoned  as  too  low,  since  the  microcytes  which 
occur  here  are  apt  to  be  missed  if  we  are  using  a  low  power.  Obviously  the 
observations  we  have  made  in  regard  to  the  variation  in  the  composition  of 


COUNTING  THE   LEUKOCYTES  283 

the  blond,  in  speaking  of  the  hemoglobin  test,  are  also  true  as  regards  the 
blood-count. 

In  practice  the  value  of  the  determination  of  the  number  of  red  blood- 
corpuscles  is  not  very  great,  but  it  is  important  in  any  careful  study  of  cases. 
This  is  obvious  if  we  realize  that  the  amount  of  hemoglobin  and  the  number 
of  blood-corpuscles  are  not  always  exactly  proportional;  that,  for  example,  a 
diminution  in  the  hemoglobin  contents  to  50  per  cent,  does  not  necessarily 
imply  a  diminution  of  erythrocytes  from  5,000,000  to  2,500,000;  they  may  be 
above  or  below  this.  We  designate  as  the  average  "value"  (V)  of  the  indi- 
vidual corpuscle  -^-,  i.  e.,  the  division  of  the  percental  hemoglobin  figure  by 
the  percental  diminution  or  increase  of  the  erythrocytes.  ["Color-index*'  i- 
the  won!  generally  used  in  America  instead  of  "value."' — En.]  If,  for  exam- 
ple, the  amount  of  hemoglobin  has  been  reduced  to  50  per  cent.,  the  erythro- 
cyte- l.eing  2,500,000  to  the  c.mm.,  the  average  "value"  has  remained  1  :  it'. 
however,  with  50  per  cent,  hemoglobin  only  200,000  red  blood-corpuscles  are 
present,  the  V  has  even  risen  to  L.25  (fS).  On  the  other  hand,  the 
••  nihil"  is  only  0.8  if  we  have  only  l<)  per  cent,  hemoglobin  and  2,500,000 
red  blood-corpuscles.  This  "  value-estimation  "  is  of  importance  fur  the  rea- 
son that  the  various  types  of  anemic  conditions  are  distinguished  by  the 
"value"  [or  color-index]  of  the  blood;  for  example,  in  chlorosis  or  in  post- 
hemorrhagic anemia  [or.  in  fact,  in  any  well-marked  secondary  or  symp- 
tomatic anemia. — Ed.],  V  is  often  decidedly  below  1.  while  in  progressive 
pernicious  anemia  it  is  frequently  decidedly  above  1. 

The  number  of  red  blood-corpuscles  to  the  c.mm.  upon  the  average  amounts 
in  men  to  5,000,000,  in  women  to  1,500,000.  [Hewes  and  other  Americans 
have  noted  that  in  healthy  American  adults  the  number  of  vr<\  cells  is  usually 
neai-  6,000,000,  often  above  that  figure. — Ed.]  In  mosl  anemic  conditions 
this  is  reduced,  and  values  below  1,000,000,  even  as  low  a.-  300,000,  have  been 
seen  without  absolutely  precluding  the  recovery  of  the  patient.  On  the  other 
hand  it  musl  1«'  emphasized  that  a  normal  number  of  erythrocytes  is  not 
proof  againsi   the  presence  of  anemia,  unless  the  amount   of  hemoglobin   i- 

also  normal. 

Under  certain  circumstances,  some  of  which  have  not  yet  been  sufficiently 
explained,  a  decided  increase  of  red  blood-corpuscles  occurs,  a  hyperglobulia. 

This  i-.  for  example,  the  case  in  the  various  form-  of  stasis  of  the  circulation. 

hut  it  i<  also  the  expression  of  an  actual  increase  of  blood  formation.  Under 
such  circumstances,  Turk,  for  instance,  found  9,150,000  erythrocytes. 

|  ( lases  of  thi~  type  were  Brei  described  by  Cabol  in  L899,  later  by  Osier  who 
noted  particularly  the  enlargement  of  the  spleen  associated  with  the  poly- 
cythemia.— Ed.  I 


III.    COUNTING   THE    LEUKOCYTES 

To  count  the  white  blood-corpuscles  we  use  a  dilution  <>f  only  1  to  io. 
which  may  he  done  in  the  large-bore  mixing  pipette  in  the  Thoma  apparatus. 
In    order    that     counting    may    he    facilitated     the    n-A    blood-corpuscles    are 


284  BLOOD   AND  BLOOD  EXAMINATION 

destroyed,  and  for  this  purpose  the  blood  is  diluted  with  0.5  per  cent, 
acetic  acid  solution.  This  process  has  only  one  disadvantage,  viz.,  that  the 
nuclei  of  erythroblasts  which  may  be  present  cannot  be  differentiated  from 
white  blood-corpuscles.  In  general,  however,  this  error  is  quite  without  im- 
portance. 

The  normal  number  of  white  blood-corpuscles  in  a  c.mm.  of  blood  varies 
between  5,000  and  10,000. 

By  an  estimation  of  the  absolute  number  of  white  and  red  blood-corpuscles 
we  simultaneously  learn  their  proportion  to  each  other,  the  importance  of 
which  we  shall  describe  somewhat  more  minutely  at  another  place. 

IV.    SPECIFIC    GRAVITY 

The  most  exact  method,  one  easily  carried  out  with  some  practice,  is  that 
of  Schmaltz.  For  this  purpose  we  require  one  or  more  drops  of  blood,  about 
0.1  to  0.2  c.c.  This  is  sucked  up  into  small  glass  capillaries  that  have  been 
previously  weighed  upon  an  accurate  chemical  scale,  noting  how  much  they 
weigh  when  empty,  and  how  much  after  having  been  filled  with  distilled 
water  at  a  temperature  of  15°  C.  Then  the  weight  of  the  tube  filled 
with  blood  is  determined,  and  the  specific  gavity  of  the  blood  is  cal- 
culated by  dividing  its  weight  by  the  weight  of  the  same  amount  of  distilled 
water. 

Hammerschlag's  method  has  been  the  most  extensively  used  from  the  fact 
that  it  does  not  necessitate  an  expensive  scale,  but  only  a  simple  aerometer 
with  divisions  from  1.010  to  1.070. 

This  process  is  based  upon  the  physical  law :  "  A  body  floats  in  a  fluid 
of  the  same  specific  gravity."  According  to  Hammerschlag  a  medium-sized 
drop  of  fresh  blood  is  permitted  to  fall  into  a  benzol  chloroform  mixture;  if 
the  blood  after  being  dropped  into  the  fluid  sinks  still  lower,  it  is  heavier 
than  the  mixture,  and  by  the  addition  of  a  corresponding  amount  of  chloro- 
form an  attempt  is  made  to  compensate  for  this.  If  the  drop  of  blood  remains 
upon  the  surface  it  is  lighter  than  its  menstruum,  which  is  now  made  lighter 
by  the  addition  of  more  benzol.  If,  finally,  the  blood  drop  remains  at  the 
height  at  which  it  is  first  dropped,  it  possesses  the  specific  gravity  of  the 
benzol  chloroform  mixture,  which  may  easily  be  read  off  by  the  aid  of  the 
aerometer.  As  the  blood  drop  under  the  influence  of  the  fluid  surrounding  it 
readily  changes  its  weight,  splitting  into  many  small  particles,  this  process 
must  be  carried  on  very  rapidly  or  fresh  drops  must  be  constantly  made  use  of. 
The  benzol  chloroform  mixture  can  always  be  utilized  for  new  estimations,  as 
it  is  readily  freed  from  blood  by  filtration. 

In  exactness,  Schmaltz's  pyenometer  is  decidedly  superior  to  Hammer- 
schlag's method. 

In  normal  males  the  specific  gravity  of  the  total  blood  is  1.059,  in  normal 
women  1.056  upon  the  average. 

In  general,  the  estimation  of  the  specific  gravity  only  complements  or  con- 
firms the  results  obtained  by  hemoglobin  estimation.  According  to  minute 
exact  investigations  the  amount  of  hemoglobin  and  of  the  specific  gravity 


SPECIFIC  GRAVITY  285 

are  equal  to  one  another,  so  that  by  this  somewhat  more  complicated  method 
of  examination  we  learn  no  more  than  may  be  more  simply  determined. 
There  are  also  tables  from  which  we  may  read  off  directly  the  specific  gravity 
of  the  blood  with  a  definite  amount  of  hemoglobin,  and  vice  versa.  This 
intimate  dependence  is  clear  without  further  explanation:  The  hemoglobin, 
as  t lie  principal  constituent  of  the  red  blood-cell,  determine-  the  greatest 
fluctuation  in  the  gravity  of  the  total  blood,  especially  since  the  fluid  of  the 
blood  is  of  an  extraordinary  constancy  in  its  composition.  Only  when  the 
specific  gravity  of  the  blood  serum  becomes  decidedly  lighter  than  the  normal 
will  the  parallelism  between  hemoglobin  and  specific  gravity  of  the  total  blood 
be  destroyed. 

Closely  related  to  the  estimation  of  the  specific  gravity  are  the  quantitative 
estimation  of  the  total  solids  and  the  estimation  of  the  amount  of  albumin 
or  nitrogen  of  the  blood.  Neither  method  has  as  yet  been  adopted  in  practice, 
partly  because  they  arc  much  too  difficult,  and  partly  because  they  do  not 
enable  us  to  form  any  opinion  which  we  cannot  otherwise  arrive  at  much 
more  readily.  It  must  be  added  that  the  result  of  the  estimation  of  nitrogen 
in  some  eases  cannot  be  utilized  at  all,  for,  besides  the  hemoglobin  and  tbe 
white  blood-corpuscles,  other  nitrogen-containing  substances,  of  other  origin, 
may  be  present  in  tbe  blood  and  in  an  indefinite  amount.  In  reviewing  what 
has  been  written  in  special  works  upon  the  subject  regarding  these  methods 
of  investigation,  we  must  say  that  they  have  added  nothing  distinctly  new 
to  hematology. 

The  investigations  which  have  been  made  with  the  total  blood  have  1 n 

extended  for  scientific  purposes  to  the  individual  constituent  parts,  also  par- 
ticularly to  the  estimation  of  the  amount  of  albumin  and  of  the  specific 
gravity.  The  separation  of  the  two  integral  parts.  BLOOD-COEPUSCLES  and 
SEBUM,  may  be  made  in  a  simple  manner  either  by  sedimentation  or  centrifu- 
gal ion.  Material  for  investigation  may  be  procured  even  from  a  few  drops 
of  Mood;  it  is  sucked  up  into  small  glass  tubes  in  which  the  serum,  at  the 
latest   in  twenty-four  hours,  may  be  spontaneously  expressed. 

A-  the  mo8l  important  resnlt  of  these  researches,  it  must  be  emphasized 
that  the  Berum  in  some  pathologic  conditions  does  not  take  part  in  the 
changes  of  the  total  blood  but   retains  its  composition.     Thus,  according  to 

Crawitz.  the  -erum   in  chlorosis  and   in   progressive  pernicious  anemia  doe-  not 

take  part,  or  to  a  very  slight  extent,  in  the  hydremia  of  the  total  blood,  and 
invariably  shows  normal  quantities  of  total  solid-.  In  chronic  nephritis,  the 
hydremia  of  the  total  blood  is  chiefly  attributed  to  the  decided  increase  of 
water  in   the  serum. 

1  shall  mention  still  other  method-  of  blood  examination,  although  they 
have  not  ;i-  yet  been  considered  of  importance  in  practice;  because  it  seems 
advisable  briefly  to  describe  -"me  conditions  of  which  mention  i-  occasionally 

made.       For,    -nice    the    purpose    of    thi-    article    i-    the    stimulation    of    nmre 

frequent   hematologic  investigation   in   practice,  we  must   consider  not   only 

those  method-  which  have  been  found  of  practical  value,  but  those  with  which. 
in  spite  of  great  efforts3  little  or  nothing  ha-  been  demonstrated  either  theoret- 
ically or  practically. 


28G  BLOOD  AND   BLOOD  EXAMINATION 


V.   ALKALINITY 


The  estimation  of  the  alkalinity  of  the  blood  must  be  first  mentioned. 
That  fresh  blood  has  an  alkaline  reaction  cannot  be  directly  determined  by 
the  use  of  litmus  paper  on  account  of  the  color  of  the  blood,  but  a  particularly 
sensitive  red  litmus  paper  must  be  moistened  with  a  dilute  sodium  chlorid 
solution,  then  the  blood  to  be  tested  must  be  dropped  upon  it  and  the  paper 
be  rinsed  again  with  a  sodium  chlorid  solution.  It  is  very  difficult  to  deter- 
mine the  degree  of  alkalinity  with  any  accuracy.  In  the  newer  methods  the 
blood  to  be  used  is  made  of  a  lacquer  color,  and  this  is  titrated  against  a 
normal  tartaric  acid  solution  with  lacmoid  paper.  For  this  purpose  we  usually 
require  somewhat  larger  quantities  of  blood,  5  to  8  c.c. ;  C.  S.  Engel  has, 
however,  constructed  an  "  alkalimeter  "  which  makes  it  possible  to  carry  out 
the  test  with  ^  c.c.  of  blood. 

How  slight  is  the  importance  of  these  investigations,  even  to-day,  is  shown 
by  the  reports  of  various  authors  that  even  the  normal  values  vary  within 
wide  limits;  for  instance,  from  203  (Canard)  to  508  (Loewy)  mgra.  NaOH 
in  100  c.c.  of  blood.  With  such  differences  in  the  normal  value,  it  is  not 
surprising  that  results  obtained  under  pathologic  conditions  give  rise  to  con- 
clusions still  less  definite.  Thus,  one  author  found  increased  alkalinity  in 
certain  diseases  in  which  another  found  decided  diminution. 

In  the  present  status  of  the  question,  we  must  be  cautious  in  introducing 
such  an  uncertain -method  of  investigation  into  practice;  for,  since  the  result 
is  finally  expressed  in  figures  which  have  a  deceptive  appearance  of  exact- 
ness, it  is  much  more  misleading  than  the  most  subjective  method  of  exami- 
nation. 

We  are  by  no  means  convinced  of  the  biologic  importance  of  the  alkaline 
reaction  of  the  blood.  Many  authors  are  inclined  to  look  upon  the  bactericidal 
properties  of  the  blood  as  bearing  a  certain  parallel  relation  to  the  alkaline 
reaction  of  the  blood,  but  are  unable  to  prove  the  correctness  of  this  view. 
Even  with  such  a  proof  little  appears  to  be  gained.  For  it  is  self-evident 
that  a  definite  degree  of  alkalinity  means  a  relative  optimum  for  bacteria, 
since  the  increase  of  alkalinity  at  once  produces  for  them  unfavorable 
conditions. 

I  must  call  attention  to  the  fact  that  Brandenburg  may  perhaps  have 
opened  a  way  out  of  these  uncertainties  by  his'  recent  investigations.  Bran- 
denburg demonstrated  that  we  must  differentiate  between  the  alkali  combined 
with  albumin  and  that  combined  with  carbonic  acid.  These  elements  can 
be  separated  from  one  another  since  the  latter  is  capable  of  diffusion,  while 
the  alkali  combined  with  albumin  is  not.  Thus  it  was  shown  that  the 
diffusible  part  of  alkali  represents  a  very  constant  value  corresponding  to 
about  60  mgm.  NaOH — while  the  non-diffusible  part  is  exposed  to  the 
greatest  variations.  It  is  now  conclusively  shown  that  under  pathological 
conditions  even  when  there  is  great  variation  of  the  total  alkalinity  from 
the  normal,  the  amount  of  diffusible  alkali — "  the  alkali  tension  " — remains 
almost  unchanged. 


SPECTROSCOPIC  EXAMINATK  >X  287 


VI.    VOLUME    OF   RED    CELLS 

Some  authors  attach  a  certain  value  to  the  determination  of  the  volume 
of  the  red  blood-cells  in  a  definite  amount  of  Mood.  For  the  correct  estima- 
tion of  this  various  instruments  have  been  invented,  and  either  those  in  which 
the  blood-corpuscles  are  separated  from  the  serum  by  centrifugation  ("  hema- 
tocrit ")  or  those  in  which  this  occurs  by  spontaneous  sedimentation,  can  be 
employed.  Every  method  should  he  rejected  in  which  salt  or  a  salt  solution 
is  used  to  prevent  the  coagulation  of  the  blood.  For  the  volume  of  red 
corpuscles  remain.-  uninfluenced  only  when  it  comes  in  contact  with  an  isotonic 
salt  solution;  as.  however,  particularly  in  pathological  conditions,  a  special 
concentration  is  isotonic  for  each  kind  of  hlood  in  each  individual  case,  the 
estimation  of  the  volume  would  first  depend  upon  a  previous  determination 
of  the  isotonic  salt  solution;  and  such  a  difficult  proee>s  can  he  of  no  use 
in  practice. 

The  method  which  we  owe  to  Koppe  is  very  valuable  because  coagulation 

is  prevented  in  the  centrifugal  tuhes  of  his  hematokrit   by  the   absolutely 

'ili  wall-  of  the  tubes.     As  the  hlood.  therefore,  remains  unmixed  we  may 

perhaps  assume  that,  after  complete  centrifugation,  the  proper  proportion  of 

plasma  and  cells  as  it  exists  in  the  blood-vessels  is  shown. 

If.  however,  the  pathology  of  the  hlood  is  investigated  by  estimations  of 
volume,  the  figures  obtained  by  these  instruments  show  nothing  that  may  he 
looked  upon  as  enriching  our  knowledge  or  promoting  our  understanding 
of  diseases  of  the  blood;  and  I  only  rein-  to  tin-  method  for  the  sake  of 
completeness,  with  the  express  statement  that  at  present  it  cannot  he  consid- 
ered a  clinical  method  of  investigation. 

VII.   SPECTROSCOPIC   EXAMINATION 

For  certain  methods  of  examination  of  the  hlood  the  u-e  of  the  spkctro- 
bcope  mu-t  he  understood,  for  in  the  recognition  of  various  hemoglobin  com- 
binations which  are  characteristic  of  certain  conditions,  particularly  of  poison- 
ing, the  spectroscopic  investigation  of  the  blood  i-  absolutely  accessary  ami 
enables  us  to  reach  conclusions  not  to  he  arrived  at  by  the  microscope  or  any 
other  method-.  The  principle  of  this  method  must  he  considered  a-  under- 
stood; hut  it  may  he  mentioned  that  in  qualitative  investigations,  a-  a  rule. 
;i  so-called  pockel  spectroscope  is  sufficient,  and  that  it  i-  well  to  place  the 
hlood  for  examination  in  watery  solutions  of  varying  concentrations  between 
two  plane  parallel  glasses. 

The  determination  of  CO-Hb  and  of  methemoglobin,  the  former  occurring 
in  carbonic  acid  poisoning,  the  second  in  various  forms  of  intoxication,  par- 
ticularly with  potassium  chlorate,  i-  of  the  greatest  practical  importance.  The 
spectroscopic  determination  of  methemoglobin,  a-  may  he  noted  from  the 
adjoining  table,  is  possible  by  characteristic  absorption  line-  (  Fig.  L6);  (The 
determination  of  CO-Hb  is  difficult  on  account  of  the  similarity  of  the  spec- 
trum with  that  of  o-ilh.    The  differentiation  is  only  certain  when  we  obs 


288 


BLOOD  AND  BLOOD  EXAMINATION 


that  the  line  of  CO-Hb  does  not  disappear  upon  addition  of  reduction  agents, 
for  example,  ammonium  sulphate,  because  CO  is  firmly  combined  with  hemo- 
globin ;  while  the  spectrum  of  O-Hb  is  changed  by  the  same  agent  to  that  of 
reduced  hemoglobin. 


I  '>  I  i  >  i  1 1  i  i  |  ,    |  1 1 1 1  |  II  1 1 1 1  i    I  I  LI  1 1 1 1. 1  1 1  1 1  II 1 1 1 1  1 1 1  M  1 1 
'to  5o  bo  70  80 

A     a      B    C  D  E  F 

FIQ_  ig, The   Various   Absorption   Spectra    of   Hemoglobin.     In  all  of  the  spectra  the 

various  Fraunhofer  lines  and  a  scale  in  millimeters  are  drawn.      (After  Landois.) 


Finally,  the  slightest  degree  of  hemoglobinemia  may  be  demonstrated  with 
certainty  by  the  spectroscope  in  those  cases  in  which  ocular  examination 
leaves  a  doubt  as  to  whether  or  not  the  serum  contains  hemoglobin. 


VIII.    AGGLUTINATIVE   REACTIONS 

To  the  law  of  immunity  which  has  made  us  acquainted  with  the  vital 
importance  of  functional  changes  in  the  blood  we  owe  a  valuable  diagnostic 
method.  We  know  that  in  the  natural  infections  of  man, 'as  well  as  in 
animal  experiment,  peculiar  changes  occur  in  the  blood  serum,  under  the 


AGGLUTINATIVE  REACTIONS  289 

influence  of  specific  bacteria  or  bacterial  toxins.  Among  these  we  may  differ- 
entiate two  classes:  The  antitoxic  sera  and  the  bactericidal  sera;  the  first 
variety  is  represented  by  the  -«'rum  containing  diphtheria  antitoxin,  the  second 
by  the  energetic  bacteriolytic  action  of  the  blood  serum  in  convalescence  from 
cholera. 

As  a  variety  related  to  the  last  group  the  agglutinating  serum  may  be 
included,  which  occurs  during  the  course  of,  and  after  recovery  from,  many 
infections.  We  are  most  familiar  with  this  condition  in  enteric  fever,  in 
which  it  first  led  to  valuable  and  practical  diagnostic  results. 

The  essential  part  of  the  phenomenon  is  that,  in  a  mixture  of  such  serum 
with  typhoid  bacilli  in  a  culture  medium,  they  are  deprived  of  their  motility 
and  clump,  i.  e..  "  agglutinate."  To  determine  tins  fact  a  few  drops  of  serum. 
1  to  2  c.c,  are  sufficient,  and  these  may  be  most  easily  obtained  by  cent  rif liga- 
tion or  sedimentation  in  thin  glass  tubes.  The  phenomenon  may  be  demon- 
strated macroscopically  as  well  as  microscopically  (Cfruber-Widal  reaction). 
In  the  former  case,  with  nutritive  bouillon  after  the  addition  of  the  serum, 
we  Bee  how  a  profuse  uniform  turbid  accumulation  of  typhoid  bacilli  clears 
completely  in  from  twelve  to  twenty-four  hours,  and  a  delicate  flocculenl 
precipitate  form-  which,  even  by  powerful  shaking  of  the  test-tube,  can  no 
longer  be  disseminated. 

The  microscopic  tesi  is  carried  out  in  the  following  manner:  A  drop  of 
the  typhoid  culture  which  is  to  be  utilized  for  the  test  is  arranged  a<  a  hanging 
drop,  so  that  we  may  convince  ourselves  of  the  active  motility  of  the  bacilli. 
If  serum  in  an  exact  proportion  is  then  carefully  added  to  the  collection  of 
bacilli,  and  one  drop  is  placed  under  the  microscope  in  a  positive  reaction. 
we  notice  even  after  a  few  minutes,  at  latest  after  a  quarter  of  an  hour,  a 
complete  cessation  of  movement,  a  clumping  of  bacteria  in  large  groups,  as 
well  as  an  indistinctness  in  their  outline-. 

[Another  method  is  the  following:  A  3-inch  test-tube  of  small  caliber 
is  carried  to  the  bedside  of  the  patient  together  with  a  clean  medicine  dropper. 
Ten  drop-  of  water  are  allowed  to  fall  from  this  dropper  into  the  test-tube. 
The  patient's  ear  is  then  punctured  in  the  ordinary  way  and  a  full  drop  of 
blood  is  sucked  into  the  dropper  and  then  expelled  into  the  water  in  the 
test-tube.  The  test-tube  is  then  corked  and  carried  to  the  laboratory  where 
the  culture  is  kept,  and  one  drop  of  the  blood  and  water  mixture  is  mixed 
with  «me  drop  of  the  culture  and  examined  between  slide  and  cover.  There 
is  no  need  of  separating  serum  and  corpuscles  in  this  test;  the  whole-blood  is 
equally  serviceable. 

for  public  health  work  the  blood  may  he  dried  on  tin  feil,  folded  in,  and 
mailed  to  the  State  Laboratory  where  dilution  is  made  by  weight.  This 
method  is  extensively  and  most  raccessfulrj  used  by  the  State  Board  of  Health 
in  M  ichigan.—  bo.  | 

The  value  of  this  reaction  test  can  only  be  properly  appreciated  if  it  is 
carried  out  with  certain  precaution-.  First,  we  must  assure  ourselves  of  the 
proper  composition  of  the  typhoid  culture  to  be  used  in  testing,  and  must  be 
Mire  that  it  i-  a  fresh  one.  not  older  than  a  day.  The  serum  requires,  as 
already  stated,  a  corresponding  dilution,  because  even  normal  serum  if  undi- 
20 


290  BLOOD  AND  BLOOD  EXAMINATION 

luted  may  cause  agglutination;  on  the  other  hand,  the  dilution  should  not 
be  too  weak,  as  the  agglutinating  substances  in  some  cases  of  enteric  fever 
are  not  present  in  very  large  amounts,  and  if  the  serum  be  too  greatly  diluted 
they  are  inactive.  It  is  best  to  begin  with  a  dilution  of  one  part  of  serum 
to  thirty  parts  of  bouillon,  and,  if  a  positive  reaction  be  obtained,  it  should 
then  be  determined  with  how  weak  a  dilution  we  can  still  secure  a  reaction. 
In  some  cases,  a  positive  reaction  has  been  obtained  even  after  concentrations 
of  1-5,000.  If  the  test  gives  a  positive  result  with  a  high  dilution,  the 
diagnosis  of  enteric  fever  is  thereby  assured,  with  the  one  limitation  that  the 
serum  may  perhaps  have  received  its  agglutinating  properties  from  a  typhoid 
fever  some  time  previously,  even  several  years  before. 

If,  however,  the  result  of  the  test  is  negative  with  a  dilution  of  1 :  30,  it  is 
well  to  repeat  it  in  the  course  of  the  disease,  daily  if  possible.  Frequently 
it  is  noted  that  in  the  early  course  of  the  disease  the  serum,  which  at  first 
showed  no  reaction  while  diluted,  gradually  in  slighter  concentration  betrays 
the  presence  of  agglutinating  substance.  But  the  diagnosis  of  enteric  fever 
cannot  be  excluded  with  certainty  even  in  case  of  a  continued  negative  result 
of  the  reaction.  The  appearance  of  the  reaction  may  be  expected  at  the 
earliest  upon  the  eighth  day  of  the  disease.1  [Since  it  is  impossible  to  fix  in 
any  way — except  arbitrarily — the  first  day  of  the  disease,  it  is  hard  to  make 
any  accurate  statement  about  the  earliest  appearance  of  Widal's  reaction. 
At  the  time  when  patients  first  consult  a  physician,  two-thirds  of  them  show 
a  positive  agglutination  reaction  in  the  blood,  but  in  a  few  it  is  delayed  as 
late  as  the  fifth  or  sixth  week,  or  it  may  never  appear.  Over  95  per  cent,  of 
cases,  however,  show  a  reaction  at  some  time  in  the  course  of  the  disease. 
Different  epidemics  vary  greatly  in  these  points,  some  showing  a  large  pro- 
portion of  early  reactions,  while  in  others  physicians  complain  of  the  high 
percentage  of  negative  reactions  in  the  earlier  weeks  of  the  disease. — Ed.] 

In  view  of  the  very  valuable  diagnostic  success  of  serum  diagnosis  in 
enteric  fever,  it  may  be  readily  understood  that  an  attempt  would  be  made 
to  reach  the  same  results  in  other  diseases,  but,  unfortunately,  there  has  been 
as  yet  no  practical  success.  Endeavors  specially  directed  to  the  recognition 
of  tuberculosis  by  its  specific  agglutinating  reaction  may  be  looked  upon  as 
futile,  since  Robert  Koch  reached  entirely  negative  results  in  this  direction. 

IX.    BACTERIOLOGICAL   EXAMINATION 

The  diagnosis  and  also  the  prognosis  may,  under  some  circumstances,  be 
helped  by  the  bacteriological  investigation  of  the  blood.     There  are  quite  a 

i  Lately  Prbscher  (Cenlralbl.  f.  Bakteriologie,  xxxi )  has  proposed  a  modification 
which  indicates  a  decided  practical  improvement.  According  to  this  it  is  particularly 
valuable  that  a  typhoid  bouillon  may  be  utilized  in  which  the  bacilli  have  been  killed 
by  the  addition  of  one  part  of  a  forty  per  cent,  formalin  to  100  parts  of  bouillon.  This 
bouillon  ma\  be  used  for  weeks  without  losing  its  agglutinating  property.  For  the 
action  of  the  serum  upon  the  bacilli  Pröscher  allows  from  one  to  two  hours  at  blood 
heat ;  for  viewing  the  serum  bouillon  mixture  which  is  kept  in  a  bowl  we  employ  a 
low  power  dry  lens   ( about  ^  enlargement ) . 


BACTERIOLOGICAL   EXAMINATION*  291 

number  of  diseases  in  which,  particularly  in  especially  severe  cases,  the 
pathogenic  agents  enter  the  blood.  Formerly  we  contented  ourselves  with  a 
microscopic  investigation  of  fresh  <>r  stained  blood  to  determine  the  presence 
of  bacteria.  Bui  this  process  should  only  be  resorted  to  for  the  determination 
of  tbe  spirilli  of  relapsing  fever,  or,  perhaps,  of  the  bacilli  of  anthrax.  In 
other  case-  it  may  lead  to  errors,  first  because  of  the  small  number  of  germs 
that  may  be  present,  ami.  secondly,  because  confusion  with  accidental  bacterial 
contaminations  may  readily  occur.  It  is  therefore  advisable  to  puncture  a 
vein  of  the  arm  under  -trict  antiseptic  precautions,  to  withdraw  1  to  2  c.c. 
of  blood,  and  to  prepare  culture-,  besl  in  bouillon,  or  to  determine  by  animal 
experiments  the  probable  presence  of  pathogenic  bacteria. 

In  this  manner  we  are  able  to  determine  with  certainty  in  the  circulating 
blood  the  presence  of  streptococci,  staphylococci,  pneumococci,  the  bacilli  of 
enteric  fever,  of  the  plague,  of  tuberculosis  and  others.  [Typhoid  bacilli  have 
repeatedly  been  cultivated  from  the  blood  of  doubtful  febrile  cases  before 
the  Widal  reaction  bad  appeared.  Eence  this  procedure  may  be  of  great 
value  in  obscure  cases.  Tbe  same  is  true  of  the  cultivation  of  pneumo- 
cocci from  the  blood  in  obscure  pneumococcus  infection-  and  ••central  pneu- 
monia.-."—  Ed.  I 

The  determination  of  the  pathogenic  agents  just   mentioned  can  only  be 
gnated  as  an  auxiliary  factor  in  diagnosis,  but  the  recognition  of  spirilli 

in  the  blood  i-  the  only  mean-  for  a  positive  diagno- 
of  relapsing  fever.     As  a  rule  ibis  determina- 
tion i-  very  easy,  for  the  peculiar  curved  form  of 

the  spirilli  (see  Fig.  17)   precludes  confusion  with 

other  organisms.     Their   Dumber   is   usually  very 

large;  our  detection  of  them  is  greatly  facilitated 

by  their  motility,  and.   finally,  they  stain   readily 

with  various  anilin  color-,  for  example,  intensely    Oq 

with  fiicb-in.  so  that  they  may  be  easily  found  in  a 

dry  preparation   even   if   present    in   the   blood  in 

very  small  cumbers. 

,,,,,.  -  ,.  .  •     ,      I  i<;.    17.  —  Relapsing 

Probably  m   no  other  disease   is  the   practical     Sl.1IU,,,.    (After v. Jaksch.) 
importance  of  blood  examination  greater  than   in 

malaria.  This  i-  naturally  not  the  place  in  which  to  describe  the  entire  devel- 
opment of  the  malarial  parasite,  nor  even  to  mention  all  of  the  varieties  which 
occur  in  the  blood,  as  a  special  article  has  I n  devoted  to  this  important  sub- 
ject.1 Here  it  need  only  be  mentioned  that,  in  many  cases,  we  should  look 
for  the  plasmodia  in  the  blood,  and  should  familiarize  ourselves  with  the  most 
important   point-  in  the  technic  of  examination. 

In  the  investigation  of  the  blood  for  malarial  parasites  for  diagnostic 
purposes,  the  Btained  dry  specimen  i-  unquestionably  the  most  suitable,  and 
we  shall  explicitly  describe  its  preparation  in  another  place.  For  when  very 
few  parasites  are  in  the  blood,  this  method  alone  assures  their  detection,  and 

i  Compare  the  article  by  Loeffler  In  the  volume  <>n  "  Infection-  Diseases." 


292  BLOOD  AND  BLOOD  EXAMINATION 

with  very  little  practice  it  protects  us  more  fully  from  error  than  an  investi- 
gation of  the  fresh  blood. 

The  withdrawal  of  blood  had  best  be  made  in  the  afebrile  period;  and 
even  here  it  must  be  borne  in  mind  that,  for  as  long  a  time  as  possible  prior 
to  this,  no  quinin  should  be  administered. 

Fixing  the  preparation  is  best  accomplished  by  the  use  of  absolute  alcohol 
for  five  minutes.  [It  seems  likely  that  all  the  fixing  methods  described  in 
this  article  will  soon  be  replaced  by  the  fixation  produced  by  methylic  alcohol 
which  is  the  menstruum  in  which  the  various  "  Romanowsky  "  stains  are  dis- 
solved. Using  Irishman's  or  Wright's  modification  of  the  Romanowsky 
method  we  fix  the  specimen  in  the  same  fluid  which  later  (when  water  has  been 
added)  stains  the  specimen.  This  saves  much  time,  trouble,  the  apparatus 
and  expense.  The  technic  is  given  in  detail  below. — Ed.]  Staining  is  best 
done  either  by  a  one- per  cent,  methylene-biue  solution,  or  by  the  Chenzinsky 
methylene-bhie  eosin  mixture  mentioned  in  another  place,  or  after  the  method 
especially  proposed  for  the  study  of  malaria  by  Romanowsky-Ziemann. 

With  an  enlargement  of  about  500  and  the  use  of  an  oil  immersion,  it  is 
not  difficult  even  for  the  novice  to  recognize  the  fully  developed  plasmodium 
within  the  red  blood-corpuscles.  First,  the  blue  tint  which  they  acquire  from 
the  methylene-blue  readily  distinguishes  them  from  the  nucleus  of  the  cell; 
this  is  an  uncommonly  delicate  sky-blue  in  contrast  with  the  darker  blue  of 
the  nucleus,  which  more  closely  resembles  the  actual  color  of  the  material  used 
in  staining.  [With  the  Romanowsky  slain  which  is  now  widely  used  in  this 
country  for  all  blood-specimens,  the  nucleus  is  colored  crimson  and  its  con- 
trast both  with  the  blue  of  the  parasite  and  the  yellow  of  the  surrounding 
corpuscle  forms  thus  one  of  the  most  recognizable  features  of  the  organism. 
— Ed.]  By  the  amount  of  pigment  the  recognition  of  the  plasmodium  is 
also  decidedly  facilitated. 

It  is  more  difficult  if  only  the  very  young  forms  of  the  plasmodia  are 
present,  those  which  are  still  very  small,  and  have  not  as  yet  formed  pigment. 
Occasionally  the  characteristic  seal-ring  shape  facilitates  their  recognition; 
frequently,  however,  the  apparently  structureless  forms  may  be  confused  with 
the  nuclei  or  the  fragments  of  a  nucleus  of  the  erythrocytes,  or  with  the  dots 
of  "  stippled  "  erythrocytes.  Here  the  character  of  the  staining  in  particular 
gives  a  point  of  support  for  their  recognition.  Observations  made  at  a  more 
favorable  time,  and  eventually  an  examination  of  the  fresh  blood  to  determine 
the  motility  of  these  bodies,  furnish  convincing  proof. 

How  important  it  is  to  carry  out  an  examination  for  plasmodia  is  shown 
by  the  fact  that,  according  to  Robert  Koch,  the  prophylaxis  as  well  as  the 
therapy  of  malaria  is  intimately  connected  with  the  results  of  the  blood 
findings. 

The  investigation  itself,  however,  is  so  simple  that  it  should  never  be 
omitted  in  any  ease  in  which  long  protracted,  perplexing  fever  is  present,  or 
in  which  the  history,  or  the  condition  of  the  spleen,  or  other  clinical  phenom- 
ena point  to  the  possibility  of  a  malarial  infection.  Especially  in  regions 
in  which  malaria  is  quite  rare  valuable  time  for  the  patient  is  frequently  lost, 
because  the  physician  has  neglected  the  examination  of  the  blood,  supposing 


BACTERIOLOGICAL  EXAMINATION  293 

a  septic  disease  or  a  tuberculosis,  etc.,  to  be  present,  and  malaria  has  not  been 
recognized  as  the  true  cause  of  the  morbid  phenomena.  |  In  this  country  the 
opposite  mistake  is  more  common.  Many  cases  of  tuberculosis  are  miscalled 
malaria  because  they  have  chills,  and  no  proper  examination  of  the  chest  or 
of  the  blood  is  made. — Ed.] 

Among  all  the  methods  of  blood  examination  used  in  the  last  decade  un- 
questionably the  most  Ear-reaching  results  have  been  attained  by  the  investi- 
gation  of  the   NORMAL  AND  PATHOLOGICAL   HISTOLOGY   of   the   blood;   this   wa- 

particularly  fostered  by  the  technic  of  the  dried  preparation  and  the  differ- 
ential stains  introduced  by  Ehrlich. 

If  a  drop  of  fresh  blood  is  placed  ander  the  microscope,  enlarged  about 
500  times  and  examined  with  an  oil  immersion  a  number  of  important  points 
may  be  observed.  There  will  first  be  noted,  provided  the  layer  of  blood  is 
thin  enough,  the  shape  of  the  red  blood-corpuscles,  their  depression,  their 
hemoglobin  staining;  by  this  method  also  the  rouleaux  formation  of  the  blood 
discs  becomes  plain.  The  structure  of  the  white  corpuscles  may  be  recognized 
by  this  simple  process,  and  various  forms  may  be  differentiated  from  one 
another. 

Tims  the  lymphocytes  are  perceived  as  cells  about  the  size  of  a  normal 
red  blood-corpuscle,  though  some  attain  double  or  even  three  times  this  size; 
their  nucleus  is  circular,  lakes  up  the  greater  part  of  the  cell,  and  is  sharply 
demarcated  from  the  narrow  protoplasmic  border  surrounding  it. 

The  majority  of  the  leukocyte-  are  conspicuous  by  their  dense,  decidedly 
refractive,  fine  granulations;  one.  two,  or  three  faint  nuclei  deposited  in  them 
may  be  recognized.  These  cells  are  twice  or  three  times  as  large  as  the 
erythrocytes.  In  a  \'<-w  of  the  leukocyte-  present  (eosinophiles)  the  granula- 
tion- an-  much  more  decidedly  refractive,  and  the  individual  granules  are 
much  coarser.  These  two  last  named  form-  are  alike  in  size,  as  well  as  in  the 
conditions  and  the  number  and  shape  of  their  nuclei. 

The  blood-plaques  are  most  easily  recognized  by  their  agglutination  in 
clumps  and  slighl  refracl  ive  power. 

Studies  of  the  more  minute  structure  of  the  leukocytes  can  only  be  made 
with  difficulty  by  this  simple  method,  as  the  form-  not  yet  described  are 
usually  only  present  in  very  small  numbers.  Moreover,  in  a  prolonged  exam- 
ination, the  blood  soon  suffers  changes  which  produce  disturbance.  In  con- 
sequence of  this  the  investigation  of  the  fresh  blood  is  of  very  little  service. 
and  we  are  usually  compelled  to  preserve  the  blood  by  a  proper  method  and 
i"  stain  if.  For  these  purposes  there  is  no  better  process  than  the  dried 
staining  proc]  88  after  Ehrlich  |e\cepi  the  methylic  alcohol  fixation  described 
below.— Ed.],  and  this  is  a-  Bimple  in  its  operation  a-  it  is  serviceable.  It 
ha-  the  practical  advantage  that  it  allow-  the  investigator  t<>  work  quite  inde- 
pendently of  the  presence  «if  the  patient,  to  choose  the  time  and  plao 
examination,  and  permits  at  any  time  a  repetition  of  the  investigation  and 
a  demonstration  of  the  result  obtained. 

The  specimen  is  made  a-  follow-:  Cover-glasses  of  about  18  mm.,  having 
a  quadrangular  -hupe  and  of  Bpecial  thinness   (0.1   to  0.08  mm.)   are  a 


294 


BLOOD  AND  BLOOD  EXAMINATION 


these  are  carefully  cleansed  in  ether  and  alcohol  so  that  fat,  fiber  and  all  parti- 
cles of  dust  are  removed.  [Water  is  sufficient  for  cleansing  cover-glasses  pro- 
vided they  are  properly  polished  with  silk  or  tissue  paper  afterwards. — Ed.] 
On  a  cover-glass  of  this  kind  a  small  drop  of  blood  which  has  exuded  from  a 
prick  of  the  finger  is  collected;  this  glass  is  dropped,  blood  side  downward, 
upon  a  second  glass,  with  the  result  that  the  blood  soon  spreads  out  spon- 
taneously in  a  thin  film  between  the  two  very  flexible  glasses  to  about  three- 
quarters  of  their  extent,  as  if  in  a  capillary  space.  After  a  complete  distribu- 
tion of  the  drop  of  blood,  the  glasses  are  removed  from  one  another  [by 
sliding  off  the  upper  of  the  two  covers  without  any  lifting  or  tilting,  but 
strictly  in  the  plane  of  their  surfaces. — Ed.],  and  the  blood  is  seen  distributed 

upon  each  in  a  uniform 
layer.  If  the  drop  taken  was 
small  enough,  the  blood  cells 
are  found  in  an  even  layer 
side  by  side  without  over- 
lapping each  other.  In  view 
of  the  fact  that  the  red 
blood-corpuscles  are  dam- 
aged with  extraordinary  ease, 
especially  by  moisture,  this 
maneuver  should  not  be  at- 
tempted with  the  unaided  hand;  for  the  moisture  of  the  tip  of  the  fingers  is 
capable  of  changing  the  outlines  of  the  red  blood-corpuscles  and  of  extracting 
their  hemoglobin.  For  this  reason,  in  the  preparation  of  these  specimens  two 
forceps  should  be  used  in  the  manner 
depicted  in  Fig.  18.  [For  any  one  whose 
fingers  are  not  habitually  and  obviously 
damp  the  use  of  forceps  is  unnecessary. 
-Ed.] 

When  the  blood  films  have  dried. 
which  usually  happens  within  twenty  to 
t hiily  seconds,  it  is  necessary  before 
subjecting  them  to  the  stain  to  fix  the 
blood  in  a  suitable  manner.  For  practi- 
cal purposes  it  is  sufficient  usually  if  the 
specimens  are  placed  for  five  minutes  in 
a  solution  of  1.0  formol  in  100  parts  of 
absolute  alcohol.  After  this  method  of 
fixation  almost  all  the  stains  which  need 
practically  be  considered  may  be  em- 
ployed. If  we  intend,  however,  to  pre- 
pare especially  beautiful  specimens,  or 
to  make  investigations  for  scientific  pur- 
poses, then  Ehrlich's  old  method — fixation  by  heat  alone — had  better  be 
utilized.  Mosl  serviceable  for  this  purpose  is  a  small  copper  kettle  (Fig. 
19)  inside  of  which  a  small  quantity  of  toluol  is  brought  to  the  boiling  point. 


Fig.  19. 


BACTERIOLOGICAL  EXAMINATION  295 

The  thin  copper  lid  of  the  kettle  will,  a  few  minutes  after  the  toluol  has  begun 
to  boil,  reach  the  temperature  of  the  boiling  point  of  toluol  (111°  C).  Upon 
the  plate  heated  in  this  manner  the  cover-glasses  with  the  dried  blood  are 
placed  for  thirty  to  sixty  seconds,  and  this  fixation  is  quite  sufficient  for  most 
of  the  staining  methods. 

Among  the  methods  of  staining  the  blood  those  of  Ehrlich  have  shown 
themselves  to  be  the  most  successful.  In  particular  his  triacid  solution,  which 
in  its  application  is  quite  simple,  brings  out  a  great  many  points,  and  fur- 
nishes reliable  conclusions.     The  formula  for  its  preparation  is  the  following: 

The  three  stains,  orange  G,  acid  fuchsin  and  methylene  green,  are  prepared 
in  saturated  aqueous  solutions,  and  are  mixed  in  the  following  amounts  and 
order  (with  thorough  shaking  during  the  process)  : 

Orange    G 13-14  c.c. 

Acid  fuchsin  6—7    " 

Aq.  dest 15 

Alcohol  15 

Methyl  given 35.5      " 

Alcohol    10 

Glycerin   10         " 

If  the  fixed  blood  preparation  is  allowed  to  floal  for  about  five  minutes 
upon  a  U-\v  drops  of  this  staining  solution,  the  staining  is  finished.  There 
is  no  danger  of  over-staining,  even  in  a  decidedly  longer  duration  of  staining. 
The  cover-glass  is  then  thoroughly  rinsed  in  water,  carefully  dried  between 
blotting  papers  and  mounted  in  Canada  balsam. 

Fot  certain  purposes,  as  we  shall  see  later  on,  this  triacid  solution  is  not 
suitable,  and  we  are  compelled  occasionally  to  use  complementary  stainings 
with  methylene-blue,  or  with  methylene-blue  eosin  mixtures.  Formulas  for 
such  stains  are  the  following : 

Vi'vy  instructive  pictures  are  obtained  if  we  stain  for  hall  a  minute  with 
a  solution  of  0.5  eosin  to  LOO  c.c.  of  a  60  per  cent,  alcohol,  rinse  in  water, 
and  subsequently  stain  for  two  minutes  with  a  watery  methylene-blue  solution 
of  l   250. 

Specimens  of  greal  clearness  and  elegance  are  obtained  by  a  careful  appli- 
cation of  the  Chenzinsky's  methylene-blue  eosin  mixture: 

Concentrated  watery  methylene-blue  solution 10  c.c. 

•  >.:>  per  cent,  eosin  solution  in  70  per  cent,  of  alcohol .  . .   20    " 
Distilled   water 40   " 

This  solution  must  he  filtered  each  time  prior  to  use;  the  staining  requires 
from  Bix  to  twenty-four  hours  and.  to  prevenl  evaporation  and  the  precipita- 
tion of  the  staining  material,  musl  be  carried  oul   in  air-tighl  closed  cups. 

By  the  aid  of  these  staining  methods  we  are  enabled  to  recognize  a  number 
of  the  peculiarities  of  the  blood  cells,  which  are  indistind  or  entirely  unrecog- 
nizable in  fresh  blood.  Some  of  the  newer,  particularly  the  so-called  "uni- 
versal," Btaina  have  such  glaring  faults  that,  at   leasi    for  the  present,  they 


296  BLOOD  AND  BLOOD  EXAMINATION 

appear  to  be  unsuitable  for  practice.  [After  using  and  teaching  Ehrlich's 
method  as  just  described  for  eight  years,  I  have  recently  discarded  it  in  favor 
of  one  of  the  "  universal  "  stains  which  our  author  here  condemns.  Leishman's 
"Romanowsky"  stain  made  up  by  Wright's  method  (see  Journal  of  Med. 
Research,  1902,  vol.  vii)  is  much  quicker  and  easier  to  use,  needs  no  fixing 
fluid  or  heating  apparatus,  and  gives  pictures  which  in  99  cases  out  of  100 
are  superior  to  those  obtained  by  Ehrlich's  method. 

The  technic  is  as  follows :  Adjust  the  cover-glass  film  in  Cornet's  forceps. 
Flood  it  with  the  stain,  using  a  medicine  dropper  and  keeping  the  bottle 
tightly  corked  when  not  in  use.  After  one  minute  add  water  drop  by  drop 
until  a  greenish  iridescent  scum  appears  on  the  surface.  About  7  drops  are 
needed  with  a  |-  inch  cover-glass.  Allow  the  stain,  so  diluted,  to  act  two 
minutes.  Wash  in  water,  and  allow  the  preparation  to  stand  one  minute  more 
in  water.    Dry  in  blotting  paper  and  mount  in  Canada  balsam. 

This  stain  brings  out  all  that  Ehrlich's  method  does  and,  besides  this,  stains 
the  blood-plates,  the  granules  of  mast-cells,  the  chromatin  of  malarial  parasites 
and  the  basophilic  granules  in  abnormal  red  cells — all  points  of  value. 

The  only  weak  point  of  the  Romanowsky  stains  is  the  deceptive  resemblance 
between  certain  megaloblasts,  certain  lymphocytes,  and  certain  myelocytes. 
In  perhaps  1  case  in  100  this  troubles  a  beginner;  in  perhaps  1  in  1,000 
it  troubles  an  expert ;  but  in  no  case  does  this  difficulty  affect  the  essentials 
— the  diagnosis,  prognosis,  or  treatment  of  the  case. — Ed.] 

In  examining  normal  blood  which  has  been  stained  according  to  these 
methods  we  note  the  following  important  peculiarities :  The  red  blood- 
corpuscles  have  been  wholly  stained  with  orange,  that  is,  with  eosin,  and  this 
causes  the  unstained  depression  which  is  free  from  hemoglobin  to  stand  out 
prominently. 

Among  the  white  blood-corpuscles  the  lymphocytes  must  be  first  mentioned 
(see  colored  plate,  Row  VII,  a  and  b).  Their  nuclei  show  the  above  described 
configuration,  and  on  staining  with  a  triacid  solution  they  are  moderately 
well  stained  with  methylene  green,  the  protoplasm,  however,  being  of  a  very 
pale  yellowish  color.  [The  nuclei  are  often  so  faintly  stained  as  to  be  nearly 
invisible.  The  protoplasm  frequently  remains  unstained  or  shows  a  faint  gray 
color. — Ed.]  In  methylene-blue  eosin  preparations  the  nucleus  is  deeply 
stained  with  the  blue  stain,  which  is  very  frequently,  however,  found  to  be 
more  marked  in  the  blue  color  of  the  rim  of  the  protoplasm.  This  is  an 
expression  of  the  fact  that  the  protoplasm  of  the  lymphocytes  is  more  baso- 
philic than  its  nucleus.  In  the  not  infrequent  cases  in  which  it  is  difficult  to 
determine  the  relation  of  a  white  blood-corpuscle  to  a  definite  cell  group,  this 
condition  is  always  a  positive  sign  that  the  cell  must  be  looked  upon  as  a 
lymphocyte;  however,  the  absence  of  this  reaction  is  not  absolute  proof  that 
the  cell  is  not  related  to  the  lymphocytes,  for,  as  may  be  noted  from  the 
colored  plate,  the  protoplasm  occasionally  shows  a  weaker  stain  with  the 
basic  staining  material  than  the  nucleus. 

The  cells  which,  in  fresh  blood,  we  have  recognized  as  finely  granular  and 
polynuclear,  are  shown,  in  staining  with  the  triacid  stain  (IX,  b)  to  have 
pale  green  colored  nuclei  and  very  fine,  almost  dust-like  granulations  of  a 


BACTERIOLOGICAL  EXAMINATION  297 

reddish  violet  color,  filling  the  entire  protoplasm.  The  granulation  owes  this 
color  to  the  chemical  action  of  a  combination  of  the  acid  fuchsia  and  the 
methylene-green  produced  by  a  "neutral"  stain;  for  this  reason  these  granu- 
lations are  designated  as  neutrophilic,  and  this  variety  of  cells  as  polynuclear 
neutrophilic  leukocytes.  As  this  granulation  only  stains  in  '■neutral"  dyes, 
it  remains  unstained  in  the  methyl ene-blue  eosin  mixtures  that  do  not  contain 
a  "neutral  "  dye  stuff,  and  we  therefore  find  in  the  polynuclear  leukocytes 
in  this  stain  an  entirely  unstained  protoplasm,  while  the  nucleus  shows  an 
intense  blue  (IX,  a). 

A  small  number  of  white  blood-corpuscles  by  their  staining  and  mor- 
phology show  a  close  relationship  to  the  group  described  above;  they  only 
differ  in  that  the  granulation  is  much  more  sparse,  and  that  instead  of  a 
polymorphic  and  intensely  stained  nucleus  a  larger,  less  indented,  quite  faintly 
stained  nucleus  is  present.  These  cells  we  designate  as  transitional  fun»* 
(see  colored  plate  VIII,  c).  They  are  the  stages  immediately  prior  to  the 
polynuclear  neutrophilic  leukocytes  which  in  part  are  formed  from  the  fol- 
lowing groups : 

Large  mononuclear  leukocytes.  This  cell  form  is  one  which  is  most  diffi- 
cult to  differentiate  from  the  lymphocytes;  nevertheless  this  differentiation 
is  absolutely  necessary.  In  the  triacid  stain  they  are  remarkable  for  their 
size,  being  three  times  as  large  as  a  normal  red  blood-corpuscle.  Their 
nucleus  is  large,  comprising  about  one-third  of  the  cell,  usually  eccentrically 
placed,  round,  of  a  pale  green  stain;  their  protoplasm  is  almost  unstained  and 
free  of  granulations  (VIII,  &).  The  cells  stained  in  methyl  ene-blue  (VIII,  a) 
are  often  decidedly  more  characteristic.  We  have  one  prominent  sign  which 
greatly  facilitates  the  differentiation  of  this  variety  of  cells  from  the  larger 
forms  of  the  lymph-cells;  namely,  that  while  (as  has  been  mentioned  above, 
and  as  may  be  noted  from  the  colored  plate)  in  the  lymphocytes  the  boundary 
between  the  nucleus  and  the  protoplasm  is  sharply  marked,  in  the  large  mono- 
nuclear leukocytes  (be  dividing  line  is  indistinct,  so  thai  frequently  we  cannot 
determine  vrhere  the  nucleus  begins  and  the  protoplasm  ends.  The  proto- 
plasm of  this  cell  variety  is  apparently  never  more  decidedly  basophilic  than 

its  nucleus. 

The  three  Lasl  named  cell  form-  constitute  an  intimately  connected  group, 
thai  is,  links  in  a  chain  of  development  the  beginning  series  of  which  are  the 
large  mononuclear  leukocytes,  and  from  these,  by  transformation  and  division 
of  the  nucleus  as  well  as  by  the  extension  of  granulations,  the  transitional 
forma  and.  later,  the  polynuclear  neutrophilic  leukocyte-,  arise. 

The  cell  forms  which  in  fresh  blood  are  conspicuous  by  their  coarse  granu- 
lations may  al-o  be  readily  differentiated  from  the  others  in  the  stained 
preparation.  Their  nuclei  stain  with  nuclear  -tains  with  medium  intensity; 
the  granulation-  which  abuo-i  completely  lid  the  protoplasm  in  the  triacid 
solution  are  orange  or  copper  color  i  X.  // ) .  and  in  eosin-containing  solutions 
they  are  stained  a  brilliant  red  (X.  " )  :  unfortunately,  in  the  reproduction 
they  are  no!  very  well  depicted.  On  account  of  this  property  of  acid  dyes 
(especially  eosin)  to  attract  these  granulations,  the  entire  cell  i-  called 
oxyphilic,  acidophilic  or  eosinophilic. 


29S  BLOOD  AND  BLOOD  EXAMINATION 

Another  variety  of  the  white  blood-corpuscles  is  the  mast-cell  (XI,  a,  b,  c), 
the  peculiarities  of  which  cannot  be  recognized  in  fresh  blood,  but  only  upon 
the  use  of  very  definite  methods  of  staining.  [Mast-cells  are  beautifully 
stained  by  the  Romanowsky  method  mentioned  above. — Ed.]  These  cells  are 
characterized  by  a  quite  coarse,  often  irregular,  granulation  which  as  a  rule 
only  partly  fills  up  the  protoplasm.  Their  distinctive  feature,  however,  is 
the  basophilic  reaction  of  the  granulations  and  their  power  to  modify  the 
color  tone  of  most  of  the  substances  that  stain  them  ("  metachromasia  "),  so 
that,  for  example,  with  kresyl-violet  E  they  stain  almost  pure  broAvn.  They 
also  differ  from  other  granulations  by  their  ready  solubility  in  water,  so  that 
they  can  only  be  stained  in  alcoholic,  not  in  watery,  stain  solutions.  There- 
fore, the  two  staining  mixtures  mentioned  above  which  are  in  most  common 
use  are  not  suitable  for  staining  the  granulations  of  the  mast-cells,  but  we 
can  best  use  for  this  purpose  alcoholic  solutions  of  methylene-blue,  dahlia,  or 
kresyl-violet  E.  [See  last  note. — Ed.]  In  the  preparations  stained  with 
triacid  the  mast-cells  are  recognizable,  since  the  insufficient  staining  of  the 
granulation  causes  the  cell  to  appear  as  if  permeated  by  vacuoles  (XI,  c). 
They  are  frequently  so  sparse  in  normal  blood  that  they  can  only  be  discov- 
ered by  examining  several  preparations. 

These  various  cell  forms  may  be  determined  in  all  normal  blood  by  the 
aid  of  different  stains,  and  in  the  adult  they  are  found  in  about  the  propor- 
tion shown  in  the  last  division  of  Table  A,  where  the  large  mononuclear 
leukocytes  and  the  transitional  forms,  on  account  of  their  close  relationship, 
are  included  in  one  group. 

In  the  arrangement  of  Table  A  the  fact  is  disclosed  that  the  lymphocytes 
occupy  a  unique  position  among  all  the  white  blood-corpuscles.  This  is 
mainly  due  to  their  origin:  They  originate  in  the  lymphatic  tissue  of  the 
body,  the  principal  mass  of  which  consists  of  the  lymph-glands ;  lesser  amounts 
of  this  variety  of  tissue  are,  however,  also  present  in  the  bone-marrow,  and  it 
therefore,  perhaps,  contributes  a  small  portion  of  the  lymphocytes  of  the  blood. 
The  groups  from  the  second  to  the  fifth,  however,  originate  exclusively  in  the 
bone-marrow;  only  under  definite  pathological  conditions  does  the  production 
of  these  varieties  of  cells  also  occur  in  other  regions.  The  point  of  origin 
of  the  mast-cells,  which  is  chiefly  in  the  bone-marrow,  must  also  be  the  con- 
nective tissue  where  they  are  formed  in  large  quantities,  particularly  in  certain 
pathological  conditions. 

A  second  comprehensive  difference  between  the  lymphocytes  and  the  five 
other  varieties  of  cells  consists  in  the  fact  that  the  latter  have  the  property 
of  active  movement  which  the  lymphocytes  do  not  possess;  we  shall  see  later 
that  this  difference  is  of  great  importance  for  the  conception  of  pathological 
processes.  [It  has  been  conclusively  shown,  I  think,  that  lymphocytes  do 
possess  the  power  of  ameboid  movement. — Ed.] 


a  r 


OS 

5  5   - 


BACTERIOLOGICAL   EXAMINATION  299 

Table  A 

THE    WHITE    BLOOD-CORPUSCLES    OF    THE    NORMAL    BLOOD 

Per  cent. 
I.  Lymphocytes   {large  and  small)  22-25 

II.  Large  mononuclear  leukocytes  ) 


u  - 


3  g.  J 

~3  .'    III.  Transitional  forms  j 

g60  I     IV.  Polynuclear  neutrophilic  leukocytes  70-72  i 

V.  Eosinophilic  leukocytes  2-4 

VI.   Musi -cells  0.01-0.5 

The  blood-plaques  are  recognizable  in  fresh  blood  by  their  lessor  size 
(1-3/*),  their  clump  formation,  and  their  slight  refractive  power;  they  stain 
a  pale  blue  in  methylene-blue  solutions,  and  in  the  triacid  stain  from  gray 
to  grayish  brown.  [In  mosi  triacid  preparations  the  blood-plates  arc  invisible. 
With  Romanowsky  stains  they  are  dark  plum  color  and  are  easily  seen. —  Ed.] 

Before  entering  upon  the  physiologic  and  pathologic  importance  of  individ- 
ual cell  forms  we  tnusi  firs!  describe  a  \\>\v  cell  anomalies.  In  different  patho- 
logical conditions  decided  changes  in  the  shape  and  size  of  the  n^\  blood-corpus- 
cles are  noted,  and  these  we  designate  by  the  term  poikilocytosis  (  Plate.  Row 
111).  The  average  normal  size  of  the  red  blood-corpuscle  is  from  8-9/*;  in 
some  conditions  of  the  blood,  besides  these  "normocytes"  there  are  also  very 
small  forms  which  may  be  only  2  to  3 p.  in  size  ("  microcytes")  :  on  the  other 
hand  we  may  observe  large  forms  which  are  frequently  from  14-15/*,  in  rarer 
cases  may  even  reach  L8,  20  and  22/*  (macrocytes,  megalocytes,  gigantocytes) . 
Besides  the  change-  in  size,  the  manifold  change-  in  the  shape  of  the  blood- 
corpuscles  are  important,  and  may  be  looked  upon  as  an  expression  «if  seg- 
mentation and  decomposil  ion. 

Occasionally  combined  with  these  pure  morphologic  changes,  bu1  quite  as 
frequently  entirely  independent  of  them,  we  note  in  the  erythrocytes  deviations 
from  normal  conditions  which  arc  shown  by  a  diminution  of  their  hemoglobin 
contents.  Fot  example,  forms  of  various  size  are  noted  in  which  the  central 
depression  is  ver$  markedly  extended  so  that  only  a  comparatively  small  part 
of  the  disc,  often  only  a  quite  narrow  rim.  appeal--  to  contain  hemoglobin; 
t.  e.,  to  stain  in  the  corresponding  solution  (see  colored  Plate,  Row  ill). 

A  diminution   in  the  amount  of  hemoglobin  of  the  individual  blood-COrpuS- 

ele  is  al-o  occasionally  shown  by  a  generally  weaker  power  of  staining. 

Besides  these  slight  deviations  in  tinctorial  properties,  the  red  blood  discs 
frequently  -how  marked  qualitative  anomalies;  for  instance,  we  note  very 
frequently  blood  discs  which  do  not  take  a  pure  -tain  with  eosin  or  orange, 
hut  a  mixed  one.  -,,  that  in  staining  with  the  triacid  -tain  they  are  more  or 
less  grayish  In-own.  in  methylene-blue  eosin  solution  from  bluish  red  to  lilac, 
and  occasionally  they  may  appear  pure  blue.  Tin-  behavior,  which  now  i- 
generally  designated  as  " polychromatophile  degeneration"  may  be  explained 

by  the    fact    that    foreign   -uh-laiice-   which   -tain   with   the  nuclear  colors  have 
['  60  72  |"  r  eint,  mi'c  normal  limit-,  in  my  opinion. — Ed.] 


300  BLOOD  AND  BLOOD  EXAMINATION 

been  deposited  in  the  plasma  of  the  red  blood-corpuscle  (see  Plate,  Bow  II). 
[There  are  many,  and  on  the  whole  convincing,  reasons  for  regarding  these 
granules  as  evidence  of  regeneration  or  of  unripeness,  but  controversy  is  still 
active  on  the  subject,  and  it  seems  best  for  the  time  to  use  some  neutral  term 
such  as  "basophilic  stippling.'' — Ed.] 

Such  a  deposit  of  substances  which,  for  example,  stain  in  methyl ene-blue 
but  not,  however,  in  the  triacid  solution,  is  found  in  a  granular  or  dust-like 
form  in  the  protoplasm  of  the  red  blood-cells,  whether  this  is  normally  stained 
or  degenerated  in  the  manner  above  described  (polychromatophilia)  (see 
Plate,  Eow  VI).  We  should  lie  cant  ions  in  assuming  the  identity  of  these 
deposits  with  the  granules  of  the  white  blood-corpuscles;  therefore  we  should 
also  avoid  the  designations  granular,  granulation,  granulated  erythrocytes, 
etc.,  and  choose  the  non-implicating  designation  "stippled  erythrocytes." 

Much  less  frequent  than  these  -mining  anomalies  of  the  red  blood-corpus- 
cles is  an  additional  one,  the  appearance  in  the  .circulating  blood  of  nucleated 
red  blood-corpuscles,  "  erythroblasts."  It  is  well  known  that  normally  in 
the  red  bone-marrow  nucleated  red  blood-corpuscles  appear.  These  are  about 
the  size  of  the  normal  non-nucleated  blood  discs,  but  contain  a  nucleus  of  an 
extraordinarily  intense  stain  and  a  protoplasm  that  usually  appears  in  the 
color  of  the  stains  that  color  hemoglobin,  more  rarely  in  that  of  polychromato- 
pbilic  degeneration.  They  are  unquestionably  the  early  stages  of  the  normal 
erythrocytes,  and  for  this  reason  are  designated  as  normoblasts  (see  Plate, 
Row  IV).  On  the  other  hand,  only  under  pathological  conditions  in  the 
adult  do  we  find  another  form  of  erythroblasts  which  are  decidedly  larger 
than  the  normal  red  blood  discs,  and  have  a  diameter  of  14,  16,  even  20  ju,  and 
more.  Their  nucleus,  as  a  rule,  is  but  feebly  stained  by  nuclear  dyes,  tbeir 
protoplasm  almost  invariably  shows  the  condition  of  polychromatophile  degen- 
eration. We  designate  this  variety  of  cells  as  megaloblasts,  or  gigantoblasts 
(see  Plate  V,  a,b),  and  recognize  in  them  the  embryonic  stages  of  megalo- 
cytes  and  gigantocytes. 

In  the  white  blood-corpuscles  changes  in  form  or  in  staining  property  are 
of  slight  importance.  It  should  be  mentioned  that  very  frequently  the  proto- 
plasm of  the  lymphocytes  at  its  border  shows  proliferation  and  segmentation, 
processes  which  indicate  a  degenerative  condition  without  our  being  able  to 
assign  to  them  definite  pathologic  importance. 

Much  more  interesting  is  the  appearance  in  the  circulating  blood  of  a  cell 
form  which,  under  normal  conditions,  is  met  with  only  in  the  bone-marrow. 
This  is  a  mononuclear  leukocyte  of  varying  size  (8  to  20  fi  in  diameter)  (see 
Plate,  Row  XII),  the  protoplasm  of  which  is  filled  by  a  dense  neutrophilic 
granulation;  Ehrlich  has  given  this  corpuscle  the  name  "  myelocyte." 

The  white  blood-corpuscles  show  variations  of  great  importance  in  their 
number,  both  as  regards  tbeir  total  number  per  cubic  millimeter  and  in  their 

proportion  to  the  red  blood-corpuscles  ("tttt)  and  particularly,  in  the  propor- 
tion of  the  individual  forms  of  the  white  blood-corpuscles  to  one  another.  The 
estimation  of  the  proportion  of  j  ^  is  possible  by  the  aid  of  Tboma's  appa- 
ratus for  counting  the  absolute  numbers;  this  may  also  be  accomplished  with 


BACTERIOLOGICAL  EXAMINATION 


301 


the  stained  dry  preparation.  For  this  purpose  we  use  the  movable  quadratic 
Ehrlich  eye-piece  (see  Fig.  20).  The  principle  of  this  diaphragm  depends 
upon  its  making  if  possible  to  count  the  red  and  white  blood-corpuscles  in 
different  large  divisions  of  the  Held  of  view,  so  that,  for  example,  the  leuko- 
cytes are  counted  in  a  field  six  or  nine  times  as  large  as  the  field  in  which  the 


I"i<;.  20.  —  Ehrlich's  Eye-piece  with  Iris  Diaphragm. 

reds  are  counted.  The  total  number  determined  after  counting  a  larger  series 
of  fields  of  the  red  is  then  directly  compared  with  the  sum  of  the  white  by 
multiplying  by  six  or  nine  A  prerequisite  for  a  correct  resull  by  this  method 
of  estimation  is  an  absolutely  uniform  layer  of  blood  upon  the  cover-glass. 

The  proportional  relation  of  the  individual  varieties  of  blood-corpuscles 
to  one  another  may  be  determined  by  a  simple  calculation  of  the  cells  when 
examining  a  <\vy  preparal ion. 

We  have  described  the  fundamental  characteristics  of  the  blood  cells  in 
their  normal  and  pathological  condition,  omitting  everything  thai  depends 
upon  purely  theoretic  investigation  and  winch  has  not  yet  been  directly  applied 
to  practice,  as  well  as  that  which  is  still  being  debated,  and  concerning  which 
the  views  of  competent  observers  are  »till  at  variance.  How  has  it  been  possi- 
ble  i'»  utilize  this  materia]  in  general  and  special  pathology? 

In  the  article  upon  Anemia  (see  this  volume)  due  ätress  has  been  laid  upon 
the  pathological  changes  which  the  red  blood-corpuscles  undergo  in  the  various 
anemia-,  and  w e  may  now  limit  ourselves  to  a  description  of  the  changes  in  the 
white  blood  cells  in  the  same  diseases. 

In  the  first  place,  a<  regards  the  appearance  of  pathological  cell  forms, 
for  the  reasons  indicated  we  have  included  only  the  myelocytes  in  our  descrip- 
tion. But  the  circumstances  under  which  these  are  found  in  the  circulating 
blood  agree  in  bo  many  point»  with  the  circumstances  under  which  the  num- 
ber of  white  blood-corpuscles   increases  or  decreases  that   they   require   no 

special  elucidation. 

Consequently,  the  most  important  chapter  in  the  pathology  of  the  white 
blood-corpuscles  Is  that  which  treat-  of  the  changes  in  their  total  number  and 
the  relative  proportions  of  the  individual  leukocyte  form-.  Since,  in  general, 
we  refer  to  the  presence  of  leukocytes  a-  leukocytosis,  an  increase  of  their 


302  BLOOD  AND  BLOOD   EXAMINATION 

total  number  we  speak  of  as  hyperleukocytosis,  and  a  diminution;,  as  hypoleu- 
Tcocytosis.  [I  prefer  the  term  "leukocytosis"  for  an  increase,  and  the  term 
"leukopenia"  for  a  decrease,  in  the  circulating  leukocytes. — Ed.]  Even  at 
the  normal,  the  absolute  number  of  white  blood-corpuscles  and  the  propor- 
tion of  their  different  varieties  show  distinct  variation ;  in  different  pathologic 
conditions,  however,  and  especially  in  infectious  diseases,  the  deviation  of  these 
conditions  from  normal  becomes  more  marked.  We  find  the  explanation  for 
this  in  the  principle  of  Chemotaxis,  according  to  which  bacteria  and  their 
products  of  metabolism,  as  well  as  numerous  other  toxic  substances,  are  capa- 
ble of  attracting  by  chemical  irritation  the  cells  which  have  accumulated  in 
the  blood-forming  organs,  a  condition  which  we  designate  as  positive  Chemo- 
taxis; on  the  other  hand  under  quite  similar  circumstances  the  leukocytes  are 
repelled  by  the  previously  mentioned  poisons,  so  that  the  number  in  the  cir- 
culating blood  is  decreased,  and  this  process  we  call  negative  Chemotaxis. 
The  self-evident  presupposition  for  this  attraction  and  repulsion  of  the  leu- 
kocytes (since  the  condition  is  a  notable  example  of  action  at  a  distance)  is  the 
property  of  the  leukocytes  to  show  active  movement.  For  this  reason  we  give 
to  this  state  the  name  active  leukocytosis. 

Active  leukocytosis  furnishes  the  most  varied  pictures,  not  only  quantita- 
tively but  qualitatively,  because  of  the  fact  that  the  chemotaxic  irritability  of 
the  different  leukocyte  varieties  shows  specific  differences.  Thus  there  are 
substances  which  only  influence  one  variety  of  cell  in  a  positive  chemotaxic 
manner,  being  inert  toward  all  others.  This  shows  itself  most  frequently  in 
a  decided  increase  of  the  polynuclear  neutrophilic  leukocytes  alone  in  numer- 
ous infectious  conditions,  as  in  septic  diseases,  diphtheria,  and  articular  rheu- 
matism; other  infections  have  a  negative  chemotaxic  property  for  this  cell 
form  so  that,  for  example,  in  enteric  fever,  we  often  find  them  decidedly 
diminished.  On  the  other  hand  the  eosinophilic  leukocytes  show  marked 
power  of  attraction  for  the  blood  in  bronchial  asthma,  in  pemphigus,  in  trichi- 
nosis, and  in  several  varieties  of  helminthiasis.  More  rare,  but  nevertheless  cer- 
tain, is  a  Chemotaxis  of  the  mast-cells  exhibited  according  to  this  principle. 

It  is  a  peculiarity  of  the  chemotaxic  reaction  that  all  leukocytes  endowed 
with  one  type  of  granulations  are  attracted  simultaneously  even  if  the  com- 
position of  the  nucleus  varies;  for  example,  the  myelocytes  react  in  the  same 
way  as  the  polynuclear  neutrophilic  leukocytes.  For  this  reason,  in  accord- 
ance with  the  variety  of  the  cell  that  is  influenced,  we  speak  of  neutrophilic 
byperleukocytosis  or  hypoleukocytosis  of  eosinophilic  or  mast-cell  leukocytosis. 

Besides  these  specific  leukocytoses,  we  diagnosticate  another  form  of  byper- 
leukocytosis which  we  designate  as  a  mixed  form,  because  in  this  all  cells  that 
are  capable  of  chemotaxic  reaction  are  increased  in  the  blood.  This  is 
myelogenous  leukemia;  we  therefore  arrive  at  the  hypothesis,  no  matter  how 
obscure  to  us  the  etiology  and  pathogenesis  of  myelogenous  leukemia  may 
still  be,  that  in  this  disease  a  toxic  substance  is  active  which  has  the  property 
of  influencing  all  myelogenous  cell  varieties  in  a  positive,  chemotaxic  manner. 

A  form  of  white  blood-corpuscles  must  still  be  mentioned  which  does  not 
possess  the  active  property  of  locomotion:  these  are  the  lymphocytes.  [See 
note  at  foot  of  p.  298.]    It  is  therefore  evident  that  this  form  is  not  subject  to 


EXPLANATION  OF  THE  COLORED  PLATE 

(All   cells  drawn  with   Lcitz  one-twelfth  oil   immersion.) 

I.  Erythrocytes,  stained  with  triacid  and  with  the  Chenzinsky  stains. 
II    Polychromatophilic  "degeneration." 
III.  Poikilocytosis;  pessary  forms. 


IV.  (a)  Normoblasts. 

(6)  Free  normoblast  nucleus. 

V.   (a)  Megaloblast. 
(6)  Gigantoblast. 

VT.  "Stippled"  erythrocytes. 

VII.   Lymphocytic. 

VIII.  Large  mononuclear  leukocytes: 
in  i  with  Chenzinsky. 
(6)  with  t  riacid. 
(c)   transitional  form. 

IX.  Polynuclear  neutrophilic  leuko 

X.  Eosinophilic  leukocytes: 
(a)  with  Chennnsky. 

ith  triacid. 

XL   Mast-iclls: 

(o)  with  methylene-blue. 

I  ith  dahlia. 
(r)  witli  triacid. 

\II    Ifyelocytes. 


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BACTERIOLOGICAL  EXAMINATION  303 

the  laws  of  Chemotaxis.  Since,  in  spite  of  this,  there  are  often  transitory  or 
permanent  variations  in  the  number  of  lymphocytes  found  in  the  blood,  these 
require  another  explanation.  We  find  this  cither  (a)  in  the  increased  pro- 
duction of  lymph-cells,  due  to  hyperplasia  or  inflammation  of  the  lymphatic 
tissue,  or  (h)  in  an  influx  of  this  variety  of  cells  by  increased  lymph  circula- 
tion. The  lymphocytes  themselves  are  entirely  passive  in  these  processes,  and 
for  this  reason  we  designate  their  increase  as  passive  leukocytosis.  Extreme 
degrees  of  this  condition  we  designate  as  lymphatic  leukemia.  (A  special  de- 
scription of  the  various  forms  of  leukemia  will  be  found  in  this  volume,  the 
article  being  by  Professor  v.  Leube.) 

I  cannot  close  this  article  without  showing  by  a  few  examples  that  the 
researches  described  here  are  of  importance  in  the  diagnosis  of  diseases  other 
than  the  actual  Mood  diseases. 

The  number  of  the  leukocytes,  for  instance.  i<  decidedly  important  in  the 
differentia]  diagnosis  of  the  infectious  diseases.  If  we  remember  how  dilli- 
cult  the  differentiation  of  enteric  fever  from  other  affections  occasionally  is. 
any  sign  which  facilitates  the  diagnosis  will  be  a  great  help.  The  affections 
which  may  he  confounded  with  enteric  fever,  such  as  osteomyelitis,  general 
sepsis,  pneumonia,  etc.,  are  characterized  by  a  decided  increase  of  the  neutro- 
philic leukocytes,  while  in  uncomplicated  typhoid  fever  this  variety  of  cell  is 
decidedly  diminished  or  is  at  most  presenl   in  only  normal  numbers. 

In  the  differentiation  of  inflammation-  of  the  cerebral  meninges,  an  ex- 
amination of  the  blood  may  often  he  of  benefit  :  and  if,  in  a  case  of  undoubted 
meningitis,  we  find  a  normal  relation  of  the  leukocytes,  the  assumption  of  the 
tubercular  form  instead  of  a  purulent  one  is  justified. 

The  occasionally  extremely  difficult  differentiation  between  scarlatina  and 
measles  may  often  he  facilitated  by  a  blood  examination  owing  to  the  fact  that 
a  distinct  diminution  of  the  polynuclear  leukocytes,  or  .-in  almosl  normal  con- 
dition of  the  Bame,  is  quite  characteristic  of  measles,  while  in  scarlatina  a 
decided  polynuclear  neutrophilic  hyperleukocytosis  is  the  rule. 

Lately  Curschmann  and  subsequent  investigators  have  reported  that  in 
numerous  cases  of  perityphlitis,  the  diagnosis  of  an  abscess  which  could  not 
he  determined  hj  palpation  was  made  from  an  increase  of  leukocyte-  to  20,000 
ami  more,  and  this  prevented  all  necessity  for  exploratory  incision.  |  *'  Lately  " 
the  Germans  have  wakened  ap  to  these  facts  which  have  been  known  and  u->'>\ 
in  America  since  described  by  me  in  1894. — Ed.]  The  subsequent  Burgical 
operation  absolutely  confirmed  the  reliability  of  this  symptom.  On  the  other 
hand,  clinician-  have  in  numerous  cases  discountenanced  a  Burgical  operation 
on  account  of  an  almost  normal  leukocyte  finding.  Here,  also,  the  further 
development  of  the  disease  justified  the  diagnosis.  Almost  as  much  impor- 
tance may  he  ascribed  to  the  phenomenon  of  leukocytosis  in  the  diagnosis  of 
abscesses  localized  elsewhere,  which  otherwise  could  not  he  determined  with 
certainty. 

In  a  case  in  which  the  diagnosis  was  otherwise  obscure,  Brown  concluded 
from  a  decidedly  marked  eosinophilic  hyperleukocytosis  thai  the  underlying 
condition  was  trichinosis;  the  further  course  of  the  disease  justified  this 
opinion. 


THE    ANEMIAS 

By    P.    EHRLICH    and    A.    LAZARUS 
Frankfort-on-Main  Charlottenburg  (Berlin) 

In  reviewing  the  earlier  literature  of  anemia,  very  exact  descriptions  of 
the  general  clinical  symptoms  may  be  found,  while  the  changes  in  the  blood 
seem  to  have  been  somewhat  overlooked.  The  object  of  this  article  is  to 
acquaint  physicians  with  the  advance  in  knowledge  along  these  lines;  points 
which  have  long  been  established  facts  will  be  passed  over  rapidly,  and  the 
special  consideration  of  hematology  will  be  our  aim. 

Easy  as  it  may  be  to  distinguish  the  different  forms  of  anemia,  mistakes 
in  their  recognition  have  sometimes  occurred,  and  do  still  occur,  chiefly  through 
a  disregard  of  hematology.  The  fact  that  there  can  be  no  anemia  without 
changes  in  the  blood  seems  to  have  been  long  ignored.  Disturbances  in  the 
circulation  of  the  blood,  especially,  lead  to  incorrect  diagnoses,  because  these 
disturbances  cause  important  clinical  symptoms  common  also  in  anomalies  in 
the  composition  of  the  blood.  Such  symptoms  are:  Intense  pallor  of  the  skin 
and  mucous  membranes,  small  pulse  and  its  increased  frequency,  and  among 
subjective  phenomena  weakness  and  vertigo.  These  acute  symptoms  appear, 
for  instance,  under  such  psychical  influences  as  fear,  terror,  etc.,  or  in  acute 
somatic  disorders  such  as  affections  of  the  stomach,  or  from  fatigue,  or  from 
excesses  in  "  Baccho  et  Vencre."  They  may  also  be  present  in  chronic  condi- 
tions, especially  in  neurasthenia,  in  gastric  affections,  and  in  heart  disease. 
Mi  stakes  are  therefore  prone  to  occur,  because  in  a  few  instances  the  symptoms 
mentioned  are  also  present  in  true  anemia. 

The  presence  of  anemia  is,  therefore,  only  positively  established  after 
blood-changes  have  been  proven.  We  never  find  that  the  blood  deviates  from 
the  normal  in  one  respect  only;  in  every  case  thorough  examination  shows  a 
group  of  changes.  Still,  a  determination  of  the  hemoglobin  alone  is  sufficient 
to  demonstrate  the  existence  or  non-existence  of  an  anemia.  We  say  a  person 
is  anemic  if  on  testing  his  blood  an  amount  of  hemoglobin  smaller  than  normal 
is  found,  and  we  adhere  to  this  designation  even  if  other  important  properties 
of  the  blood  and  the  clinical  symptoms  appear  entirely  normal.  On  the  con- 
trary, when  a  patient  has  the  general  clinical  symptoms  of  anemia  while  his 
blood  shows  a  normal  percentage  of  hemoglobin,  we  do  not  call  him  anemic. 
In  practice,  every  case  of  anemia  is  identical  with  oligochromemia. 

The  reduction  of  hemoglobin  may  be  due  to  the  fact  either  that  too  little 
is  formed  or  too  much  consumed.  A  formation  of  hemoglobin  that  does  not 
keep  pace  with  the  normal  consumption  may  be  either  the  expression  of  an 
304 


SIMPLE   ANEMIA  305 

affection  of  the  hematopoietic  organs,  or  in  consequence  of  the  fart  that  too 
little  material,  or  an  inferior  material,  is  at  the  disposal  of  these  organs. 

An  exaggerated  consumption  of  hemoglobin  takes  place  in '  hemorrhages 
and,  indirectly,  also  in  wasting  processes  of  all  kinds.  The  processes  of  blood 
regeneration  and  blood  consumption  are  so  intimately  related  that  a  disturb- 
ance of  one  of  these  processes  is  likely  to  bring  about  a  disturbance  of  the  other. 

Often  the  blood  regeneration  i<  only  relatively  insufficient;  that  is,  the 
blood-forming  organs,  especially  the  bone-marrow,  furnish  less  blood  than  is 
required  for  the  momentarily  and  abnormally  increased  demand.  In  these 
cases  it  often  occurs  that  the  hematopoiesis  is  more  considerable  and  innre 
energetic  than  in  health,  entire  portions  of  the  bone-marrow,  physiologically 
passive,  now  becoming  active;  the  consumption  of  blood  may.  however,  re- 
main so  great  that  even  an  increased  production  does  not  maintain  the  balance. 
In  the-e  cases,  whether  the  work  of  the  blood-making  organs  i-  absolutely 
increased  or  diminished,  the  amount  only,  not  the  manner,  of  blood  formation 
is  changed. 

On  the  contrary,  we  see  conditions  in  which  the  type  of  blood-formation 
in  larger  or  smaller  regions  of  the  bone-marrow  has  changed,  and  hemato- 
poiesis has  assumed  a  type  which  is  abnormal  in  the  adult  organism. 

Those  anemir  conditions  in  which  blood  restitution  takes  place  according 
to  a  normal  type  are  called  simple  anemias;  and  those  in  which  the  pro, .ess 
is  partially  or  wholly  different  from  the  normal  type  which  will  be  considered 
more  in  detail  later,  are  called  progressive  pernicious  anemias.  [The  old 
term,  "simple  anemia,"'  to  which  Ehrlich  here  revert-,  dor-  nol  seem  to  me 
likely  to  come  back  into  use.  It  seem-  mo-t  reasonable  to  retain  our  preseni 
current  term,  "secondary  or  symptomatic  anemia"  for  trouble  of  this  type, 
and  to  use  the  term-,  "pernicious  anemia"  and  "chlorosis"  with  the  con- 
sciousness thai  they,  too,  are  secondary,  but  secondary  to  a  cause  which  in  mosl 
ca-e-  i-  wholly  unknown. —  Ed.] 

SIMPLE    ANEMIA 

A-  a  resull  of  extensive  observations  of  the  blood  changes,  and  of  supple- 
mentary studies  of  the  changes  in  the  bone-marrow,  we  know  that  in  by  far 
the  larger  Dumber  of  ca-e-  <>f  anemia  the  normal  mode  of  blood  regeneration 
i-  preserved;  hence,  these  are  classed  as  simple  anemias. 

The  causes  of  simple  anemia  are,  lir-t  of  all.  acute,  subacute,  and  chronic 
posthemorrhagic  condition-.  The  supervention  of  anemia  in  these  instances 
from  the  loss  of  considerable  Mood  i-  readily  understood. 

Many  constitutional  or  organic  diseases  lead  to  simple  anemia,  either  by 
reducing  the  appetite,  or  by  the  loss  of  blood  and  tissue-juices,  bul  especially 
through  suppuration  and  albuminuria.  Poisons  also  play  an  important  röle. 
Here  the  large  group  of  autointoxication-  play  a   pari    and  another  da  mag» 

dour  by  toxic  substances  developed  by  bacteria  and  other  parasites.     We  may 

explain  in  two  ways  the  effeci  which  brings  about  the  anemia  without  being 
able,   in    the  special    instance,   to  determine   with   certainty   which   of   the   two 

acthe  causes,  or  whether,  perhap-,  both  together,  have  been  operative.     Some 

21 


306  THE  ANEMIAS 

of  the  poisons  appear  to  destroy  the  blood  directly;  others  to  diminish  or  to 
change  the  function  of  the  hematopoietic  organs. 

Excluding  the  diseases  accompanied  by  suppuration,  bleeding,  and  gan- 
grene, a  few  others  deserve  especial  mention  as  producing  simple  anemia. 
Such,  for  instance,  are  chronic  digestive  disorders,  malignant  tumors,  scrofu- 
losis,  syphilis,  malaria,  and  the  different  forms  of  helminthiasis. 

In  addition  to  the  symptoms  of  the  diseases  which,  according  to  the  old 
terminology,  were  called  "secondary  anemia,"  the  symptoms  of  simple  anemia 
may  be  found  in  cases  which  are  apparently  "idiopathic.*'  They  are  the  con- 
sequence of  faulty  hygienic  conditions,  among  which  unsatisfactory  nutrition 
plays  the  greatest  role,  and  it  may  here  be  remarked  that  food  which  leads 
to  a  reduction  in  the  percentage  of  hemoglobin  need  not  necessarily  be  insuffi- 
cient in  quantity  but  it  is  lacking  in  iron  and  albuminous  substances.  [That 
faulty  nutrition  is  a  cause  of  anemia  seems,  of  course,  most  plausible,  but 
definite  evidence  for  it  is  so  far  wanting. — Ed.] 

But,  whatever  the  cause  of  the  anemia  in  individual  cases  may  be,  no  dif- 
ference is  to  be  noted  in  its  essential  results,  the  changes  in  the  blood,  or  in 
their  main  clinical  symptoms. 

The  most  important  symptom  is  the  reduction  in  hemoglobin  ;  this  not 
only  characterizes  the  disease  as  anemia,  but  also  gives  us  information  as  to 
the  degree  of  the  morbid  changes.  Cases  vary  greatly  in  this  respect,  and  vary 
without  any  apparent  relation  to  the  etiology.  We  meet  with  cases  of  "simple 
anemia  "  in  which  the  values  are  but  slightly  below  the  normal.  To  this 
class  belong  also  cases  which  show  20,  15  and  even  only  10  per  cent,  of  the 
normal  amount  of  hemoglobin. 

In  the  mild  cases  of  simple  anemia,  the  red  blood-corpuscles  differ  little 
from  those  of  normal  blood.  In  cases  somewhat  more  serious,  deviations 
from  the  normal  number  and  morphological  changes  are  observed.  In  ex- 
treme cases  the  number  of  red  cells  may  amount  to  less  than  10  per  cent,  of 
the  normal ;  50  per  cent,  is  by  no  means  rare. 

For  the  numerical  relation  between  the  percentage  of  hemoglobin  and  the 
blood-corpuscles  in  simple  anemia,  the  etiology  seems  to  be,  to  some  extent,  a 
determinative  factor.  Parallel  deviations  of  both  values  from  the  normal  are 
often  seen;  for  instance,  a  reduction  of  30  per  cent,  in  the  amount  of  hemo- 
globin corresponds  to  a  reduction  of  30  per  cent,  in  the  number  of  red  corpus- 
cles. After  hemorrhages,  however,  we  find  that  the  amount  of  hemoglobin  is 
considerably  less  than  the  corresponding  red  corpuscle  count;  and  in  cases  of 
uncomplicated  chlorosis,  the  parallel  is  disturbed  in  the  sense  that  the  number 
of  red  corpuscles  is  often  nearer  the  normal  than  the  hemoglobin  value. 

The  morphological  changes  of  the  erythrocytes  in  simple  anemia  affect 
their  size  and  their  shape.  We  find  that  the  individual  red  corpuscles  show 
considerable  difference  in  size;  being  mostly  smaller  than  normal.  Increase 
in  size  is  rare,  and  is  then  but  slight.  The  shape  of  the  red  corpuscles  is  fre- 
quently more  or  less  distorted  and  deformed.  These  conditions  of  deviation  in 
size  and  shape  are  designated  "  poiTcilocytosis."  Milder  degrees  of  simple 
anemia  do  not  show  it,  but  the  degree  of  poikilocytosis  corresponds  to  the 
severity  of  the  anemia. 


SIMPLE  ANEMIA  307 

The  reduction  in  the  hemoglobin  value  of  the  individual  corpuscle  is,  in 
some  cases  of  simple  anemia,  very  striking.  This  can  he  seen  in  fresh  blood, 
but  better  in  the  dry  stained  preparation,  from  the  fact  that  a  larger  area 
of  the  center  remains  unstained  than  would  correspond  to  the  physiological 
depression  of  the  corpuscle.  In  some  forms  only  a  ring  of  stained  portion 
may  he  seen  (pessary  forms). 

Furthermore,  the  red  corpuscles  often  manifest  under  the  microscope  a 
change  in  reaction  to  the  usual  stains.  This  change  is  known  as  "anemic 
or  polychromatophilic  degeneration.'91  It  may  be  recognized  from  the  fact 
that  the  hemoglobin  of  the  corpuscles  does  no1  assume  the  pure  color  of  the 
stain  (eosin,  orange),  but  a  mixed  color  (blue-red  in  the  methylene-blue  eosin 
solutions,  grayish-yellow  with  the  triacid  solutions).  These  changes  are  often 
wry  pronounced  even  in  the  mildest  degrees  of  simple  anemia. 

A  rare  occurrence,  which  is  probably  characteristic  only  in  especial  forms 
of  simple  anemia,  is  the  presence  of  granular  or  punctiform  deposits  in  the 
protoplasm  of  the  erythrocytes  ("stippled  erythrocytes");  these  are  most 
apparent  when  stained  with  methylene-blue.  They  are  found  especially  in 
lead  anemias,  even  in  the  mild  grade-,  and  also  in  malarial  anemias.  In 
Bimple  anemia-  of  other  etiology,  even  in  very  grave  cases,  they  are  commonly 
absent,  so  that  to  a  certain  extent  specific  significance  may  be  attached  to 
them.  |  The  universally  applicable  Romanowsky  stains,  described  and  recom- 
mended above,  bring  out  the  .-tippling  beautifully. — Ed.] 

Of  great  importance  in  the  diagnosis  of  the  differenl  kinds  of  anemia  is 
the  fact  that  in  the  circulating  blood  nucleated  red  corpuscles  of  the  same 
kind  as  those  found  in  the  normal  red  marrow  ("normoblasts")  sometimes 
appear.  Such  cells  are  noted  in  comparatively  few  cases  of  simple  anemia. 
\\e  find  normoblasts  with  fair  regularity,  though  usually  only  transitorily,  in 
post-hemorrhagic  condition-,  and  sometimes,  in  these  cases,  in  quite  large 
numbers.  Their  appearance  proves  an  increase  in  intensity  of  the  activity  of 
the  bone-marrow,  and  in  extent  of  marrow  which  is  active;  for  the  clinical 
phenomenon  corresponds  anatomically  to  a  more  or  less  decided  transformation 
of  quiescent  fat  marrow  into  functioning  in]  marrow,  and  an  especially  marked 
richness  of  these  portions  in  normoblasts.     We  must  emphasize  the  fact  that 

the  appearance  of  normoblasts  in  the  blood  i-  in  no  relation  to  the  severity 
of  the  anemia;   sometimes   they  are   found    in   the  mildest    condition-,  and   are 

often  looked  for  in  vain  in  the  severest.  Except  in  acute  post-hemorrhagic 
anemia  their  number  i<  always  -mall — so  that  only  one  nucleated  corpuscle  is 
found  to  one  thousand  and  more  non-nucleated  red  blood-corpuscles. 

Besides  the  presence  of  normoblasts  microbkuts  are  sometimes  noted. 

Other  alteration-   in   the  properties  of  the  blood   are  al-o   found    in   simple 

anemia,  always  in  the  direction  of  a  reduction  in  the  values.     This  is  true  of 

the  SPECIFIC  GRAVITY  OP  THE  H60D,  it-  total  solids,  and  the  amount  of  nlhii- 
miii  il  contains;  the  reduction  18  the  more  pronounced  the  greater  the  devia- 
tion of  th..  hemoglobin  from  the  normal. 

The  WHITE  COBPDBOLES  in  simple  anemia   pre-ent   nothing  that    Lfl  cbarac- 

'  Sit  article,  "  Blood  and  B] I  Examination." 


308  THE  ANEMIAS 

teristic.  In  one  case  we  may  find  a  normal  number  of  their  different  varieties, 
in  another  ca.se  a  marked  neutrophilic  hyperleukocytosis  may  be  present,  in  a 
third  a  hypoleukocytosis,  or  an  increase  in  the  number  of  lymph-cells,  etc.  So 
many  factors  influence  the  condition  of  the  leukocytes,  that  in  the  multitu- 
dinous cases  of  simple  anemia  due  to  causes  or  complications  differing  from 
one  another,  no  uniform  picture  can  be  described. 

Summarizing,  we  may  say  that  the  most  important  and  essential  symptoms 
of  the  blood-changes  in  simple  anemia  are  a  diminution  in  the  hemoglobin 
percentage  and  in  the  number  of  red  blood-corpuscles,  poikilocytosis,  and  the 
changes  in  the  staining  reaction.  By  attending  to  these  factors  in  each  indi- 
vidual case  we  can  decide  whether  or  not  it  belongs  to  the  simple  anemias, 
and  how  grave  the  prognosis  is. 

The  general  clinical  symptomatology  of  anemic  conditions  exhibits  a  few 
traits  so  characteristic  as  to  make  them  in  most  cases  readily  recognizable  even 
without  an  examination  of  the  blood.  Owing  to  their  wide  distribution,  they 
are  so  well  known  to  physicians  that  a  brief  reference  to  them  will  suffice. 

The  pallor  of  the  skin  and  of  the  mucous  membranes  is  an  obvious  conse- 
quence of  the  diminished  hemoglobin  percentage  of  the  blood.  It  is  often 
intensified  by  a  permanent  constriction  of  the  peripheral  blood-vessels.  The 
same  causes  lead  to  a  lessened  capacity  for  muscular  work,  and  readily  produce 
sensations  of  weakness  and  fatigue.  The  most  vital  internal  organs  must  also 
suffer  in  consequence  of  a  reduction  in  the  value  of  the  nutrition;  and,  in 
severe  cases,  all  physical  and  psychical  functions  are  below  par. 

It  is  surprising  that,  in  anemic  people,  the  general  metabolism,  even 
the  interchange  of  gases,  is  not,  as  a  rule,  reduced ;  whereby  we  may  conclude 
that  if,  in  some  cases,  these  functions  are  abnormal,  it  is  due  not  to  the  anemia, 
but  to  some  special  cause  or  complication. 

Even  in  severe  cases,  the  adipose  tissue  is  well  preserved  unless  a  loss  of 
flesh  follows  in  consequence  of  some  special  circumstances  (as  severe  nutri- 
tive disturbances).  This  is  a  striking  phenomenon  for  which  no  satisfactory 
explanation  has  been  given;  it  was  formerly  attributed  to  a  reduction  in  the 
oxidation  processes,  but  this  is  usually  not  present  at  all ;  and  the  reduction 
in  muscular  activity  and  other  functions  is  not  sufficient  cause. 

Eelated  to  this  phenomenon  is  fatty  degeneration  of  some  of  the  organs, 
especially  of  the  muscles  and  the  circulatory  system.  Fatty  degeneration  and 
fatty  infiltration  are  chiefly  found  in  the  muscles  of  the  heart,  in  the  muscles 
of  the  eye,  and  the  intima  of  the  blood-vessels. 

To  the  fatty  degeneration  of  the  endothelial  cells  of  the  blood-vessels  may 
be  attributed  the  fact  that  in  many  anemic  conditions  a  general  hemorrhagic 
diathesis  develops,  which  not  infrequently  combines  with  the  primary  dis- 
ease to  form  a  vicious  circle.  By  their  localization  in  the  organs  of  special 
sense,  hemorrhages  of  the  eye  and  the  ear  are  especially  alarming,  and  lasting 
injury  with  total  destruction  of  sight  and  hearing  has  been  observed  in  severe 
cases  of  simple  anemia.  On  this  occasion  we  consider  it  our  duty  to  differ 
with  the  widespread  opinion  that  the  symptom  of  retinal  hemorrhage  in  anemic 
conditions  belongs  exclusively  to  progressive  pernicious  anemia. 


SIMPLE  ANEMIA  309 

The  diagnosis  of  simple  anemia,  therefore,  is  often  easily  made  from  its 
most  manifest  features.  The  careful  physician  will,  however,  make  a  Mood  ex- 
amination, or  at  least  a  test  for  hemoglobin,  even  in  cases  where  a  glance  is  suf- 
ficient to  show  that  he  is  dealing  with  anemia.  In  this  way  alone  can  we 
determine  with  certainty  what  part  vasomotor  influences  play  in  shaping  the 
disease.  This  alone  will  assure  us  that  the  supposition  of  anemia  is  not  un- 
founded ;  and  if  the  test  shows  a  reduction  we  have  then  positive  information 
regarding  the  degree  of  anemia.  Moreover,  in  every  ease  of  severe  anemia,  a 
microscopic  examination  of  a  stained  specimen  of  the  blood  is  absolutely  acces- 
sary in  order  to  make  the  important  differential  diagnosis  between  simple  and 
progressive  pernicious  anemia. 

The  prognosis  depends,  in  the  first  place,  upon  the  cause  of  the  disease. 
If  this  can  lie  removed  there  is  a  good  prospeet  of  a  eure.  Under  snch  cir- 
cumstances, even  in  the  severest  cases  in  which  the  hemoglobin  and  the  number 
of  red  corpuscles  amount  to  only  10  per  cent,  of  the  normal,  we  have  known 
casee  of  simple  anemia  to  terminate  in  complete  recovery. 

The  treatment  of  simple  anemia  must  in  the  first  place  be  directed  to  the 
cause.  In  numerous  cases  in  which  the  cause  is  found  and  removed,  ;i<,  for 
instance,  continually  recurring  hemorrhages  in  the  intestinal  tract,  worms, 
improper  hygienic  condition-,  etc.,  no  special  treatment  of  the  anemia  is  neces- 
sary after  the  removal  of  the  cause;  for  spontaneously  the  blood  returns  to  its 
normal  state. 

When  causal  treatment  is  impossible,  or  when  it  fails  to  influence  the 
anemia  beneficially,  attention  must  be  paid  to  the  symptoms  of  anemia  a-  such. 
In  tin'  great  majority  of  cases,  medication  is  far  superior  to  any  other  mode 
of  treatment.  Inni  and  arsenic,  separately  or  combined,  lend  a  powerful 
stimulus  to  blood  production,  and  after  their  rational  administration,  often 
even  in  a  frw  week-,  the  morbid  changes  in  the  blood  and  in  the  general  con- 
dition disappear,  and  make  way  for  a  restoration  to  health.  The  choice  of 
the  special  preparation  i-  essentially  unimportant;  the  main  poinl  is  to  con- 
tinue the  treatmenl  long  enough,  and  to  administer  sufficiently  large  doses. 
The  general  rule  that  0.1  gram  of  iron  is  to  he  given  pro  «lie  may  serve  as 
a  criterion  for  the  administration  of  special  iron  preparations,  organic  or 
inorganic.  The  dose  of  arsenic  varies  widely,  and  it  musl  he  determined  by 
the  individual  tolerance.  Usually  we  succeed  besl  if  we  administer  :'■  to  .">  milli- 
grams of  arsenioua  acid,  divided  info  several  doses,  properly  diluted  and  given 
on  a  full  stomach.     The  drug  Bhould  be  continued  for  a  long  while,  even  after 

the  normal  status  ha-  been  reached. 

But  there  are  other  anemic  conditions  in  which  iron  and  ar-enic  give  unsat- 
isfactory results,  or  are  <»f  no  use  whatever.  Here  dietetic  "nil  physical  therapy 
must  be  resorted  to.      As  the  metabolism  <>f  anemia  doe-  not  deviate  from  (he 

normal,  the  normal  diet  of  healthy  people  may  be  allou.d.  Theoretically,  pref- 
erence ha-  been  given  to  food  rich  in  iron    lineal.  Volk  of  egg,  spinach,  apple-, 

v\c).  often,  however,  owing  to  th«'  special  peculiarities  of  a  given  case  (for 
instance,  in  cases  complicated  with  gastro-intestinal  affections)  special  modifi- 
cations of  the  diel   mu-t   be  made  which  cannot   he  here  considered. 

Among  the  general  auxiliary  measures  in  the  treatment  of  anemics,  n 


310  THE  ANEMIAS 

physical,  mental  and  psychical — must  be  accorded  the  first  place.  In  this  con- 
nection, certainty  in  diagnosis  will  aid  materially  in  the  choice  of  treatment; 
for  instance,  the  pale  neurasthenic,  not  really  anemic,  needs  considerable  phys- 
ical exercise;  while  the  muscular  activity  of  a  true  anemic  must  be  limited 
as  much  as  possible. 

Modem  hydrotherapy  has  gradually  acquired  a  prominent  place  in  the 
treatment  of  anemia;  but  we  must  always  bear  in  mind  that  the  withdrawal 
of  too  much  bodily  heat  is  to  be  avoided,  because  all  anemics  are  sensitive  to 
cold.  Cold  applications,  such  as  cold  ablutions  with  friction,  or  partial 
douches  of  short  duration,  are  best  given  in  the  morning  immediately  on  ris- 
ing— for  then  the  redilatation  of  the  cutaneous  blood-vessels  takes  place  pleas- 
antly and  actively  after  the  patient  returns  to  his  bed.  Here,  too,  we  must 
remember  the  distinction  between  the  treatment  of  anemics  and  of  pseudo- 
anemics;  the  latter  have  a  perfectly  normal  composition  of  the  blood,  and 
only  suffer  from  an  abnormal  contraction  of  the  peripheral  blood-vessels. 

In  protracted  cases,  a  change  of  climate  is  frequently  very  beneficial,  and, 
particularly  in  excessive  anemia,  a  sojourn  in  the  mountains  of  medium  alti- 
tude. More  robust  patients  may  be  sent  with  advantage  even  to  high  moun- 
tainous regions,  which  often  powerfully  stimulates  the  regeneration  of  the 
blood. 

In  most  cases  of  severe  anemia,  a  sojourn  at  the  seashore  is  not  to  be 
advised;  in  moderately  severe  cases  it  is  to  be  recommended.  Great  caution 
must  be  exercised  in  the  use  of  sea-baths,  as  they  sometimes  aggravate  anemia. 

PROGRESSIVE   PERNICIOUS   ANEMIA 

Progressive  pernicious  anemia  must  be  distinguished  from  other  anemic 
conditions  because  in  blood-regeneration  it  presents  a  most  striking  peculiar- 
ity. In  opposition  to  the  process  in  simple  anemia,  in  progressive  pernicious 
anemia  blood-regeneration  in  larger  or  smaller  regions  of  the  bone-marrow 
takes  place  in  a  manner  different  from  the  physiological.  In  the  blood-form- 
ing organs  and  in  the  circulating  blood  cells  we  note  cells  which  are  never 
found  in  the  healthy  adult  organism.  Since  these  cells  are  found  physio- 
logically in  the  embryonal  life  of  man,  we  speak  of  a  "  reversion  of  blood- 
formation  to  the  embryonal  type." 

Before  accurate  study  of  the  changes  in  the  blood  and  in  the  bone-marrow 
had  been  made  possible,  the  consideration  of  this  particular  form  of  anemia 
as  a  special  type  was  based  upon  a  more  negative  foundation.  If  the  symp- 
toms of  severe  anemia  were  found  without  a  distinctly  palpable  cause,  the 
disease  was  considered  idiopathic,  and  was  designated  progressive  pernicious 
anemia.  Almost  always  in  such  cases  we  observed  in  the  blood  the  changes 
alluded  to,  which  are  to  be  accurately  described  later  on,  and  thus  these  posi- 
tive signs,  particularly  as  they  are  regarded  as  the  expression  of  marked  trans- 
formation in  the  body,  are  almost  universally  recognized  as  the  important 
differential  diagnostic  points. 

The  theory  of  the  "  primary  "  nature  of  progressive  pernicious  anemia  was 
shattered  in  the  course  of  time  by  numerous  experiences,  and  this  aided  us 


PROGRESSIVE    PERNICIOUS  ANEMIA  311 

in  arriving  at  our  present  standpoint.  To-day  we  know  that  progressive  per- 
nicious anemia  may  undoubtedly  often  follow  other  diseases,  and  not  as  an 
independent  disease,  but  only  as  a  symptom;  as,  for  instance,  in  the  case  of 
diabetes.  We  shall  now  briefly  describe  what  has  been  demonstrated  with 
certainty. 

The  best  illustration  of  severe  anemia  which  we  possess  is  the  case  of 
individuals  who  harbor  the  bothriocephalic  latus  in  their  intestines.  Not- 
withstanding all  the  controversies  on  this  subject,  there  can  be  no  doubt  that 
tins  worm,  living  or  dead,  may  produce  the  most  severe  anemic  conditions,  and 
that  this  bothriocephalus  anemia  is  a  true  progressive  pernicious  anemia.  We 
understand  fully  the  mode  of  action  of  this  parasite,  and  may  regard  it  as 
proven  that  the  disease  is  due  to  toxic  substances  that  have  a  hemolytic  effect, 
and  thus  cause  anemia.  Further  it  may  also  be  assumed  as  likely  that  the 
parasite  changes  the  activity  of  the  bone-marrow  in  a  peculiar  way.  The  in- 
contestable fact  that  a  very  large  number  of  people  are  afflicted  with  bothrio- 
cephalidse  without  becoming  anemic  may  be  explained  in  different  ways.  In  the 
first  place,  there  may  be  a  difference  in  the  degree  of  virulence  of  the  toxins; 
or,  again,  a  difference  in  the  susceptibility  of  the  host.  For  there  is  no  doubt 
that  individuals  of  one  species  may  possess  a  very  different  susceptibility  to 
the  same  poison;  for  example,  the  susceptibility  of  rabbits  to  crotin  has  lately 
been  proven  to  .-bow  enormous  variations.  Finally,  the  explanation  of  a  grad- 
ual autoi minimization  to  the  toxin  is  quite  reasonable. 

Leaving  now  the  consideration  of  bothriocephalus  anemia,  which  is  al  pres- 
ent understood,  we  may  say  that  all  that  i-  known  of  the  presumable  causes 
of  progressive  pernicious  anemia  may  thus  be  summarized:  "The  same  dele- 
terious agents  which  are  capable  of  producing  a  'simple*  anemia  may  also 
develop  the  progressive  pernicious  form."  Why  apparently  identical  causes 
may  in  some  instance-  produce  the  common  simple  anemia  and  in  others  the 
comparatively  rare  progressive  pernicious  anemia  we  do  not  as  yet  know. 

In  considering  the  symptoms  of  progressive  pernicious  anemia,  changes 
hi  the  blood,  especially  morphological  alterations,  claim  our  closest  at- 
tention. 

In  a  typical,   well-defined   case  of  progressive  pernicious  anemia,   the   first 

glance  al  a  good  stained  preparation  is  sufficient  to  distinguish  it  from  simple 
anemia.  We  lind  that  the  majority  of  erythrocytes,  or  at  Leasl  a  targe  number 
of  them,  have  a  diameter  lamely  above  the  normal.  1  .">  to  L8 ju  (megalocytes) 
and,  by  their  >tain.  these  cell-  disclose  to  us  a  -reat  richness  in  hemoglobin. 

On    repealed   examination,   we  almost    always    lind    some   megaloblast8}   i.e.. 

erythrocytes  with  nuclei,  the  predecessors  of  the  megalocytes.  Except  in  the 
worsl  stages  of  the  disease,  the  number  of  megaloblasts  is  always  very  Bcant. 
|  The  number  of  megaloblasts  usually  exceeds  the  number  of  other  erythroblasts, 
but  presents  no  close  parallelism  with  the  severity  of  the  clinical  manifesta- 
tions or  with  the  intensity  of  the  anemia.  ll  i-  true  that  in  m08t  cases  the 
number  of  megaloblasts  increases  a-  the  Bymptoms  are  aggravated,  and  dimin- 
ishes in  the  remissions  of  the  disease.  But  to  tin-  rule  there  are  many  excep- 
tions.—Ed.]  Besides  megaloblasts,  normoblasts  and  microblasts  are  also  to 
be  found,     of  non-nucleated  red  corpuscles,  besides  megalocytes,  we  also 


312  THE  ANEMIAS 

cells  of  normal  size  or  smaller;  the  smallest  forms,  the  microcytes,  are  fre- 
quently observed. 

All  other  peculiarities  of  simple  anemia  are  to  be  found  in  progressive 
pernicious  anemia:  Poilcilocytosis,  polychromatophilic  degeneration,  and 
"stippled"  erythrocytes;  contrary  to  the  rule  in  simple  anemia  stippled  eryth- 
rocytes are  found  with  great  regularity  in  progressive  pernicious  anemia. 

The  red  corpuscles  arc  always  noticeably  reduced,  often  to  the  low  figure 
of  20  per  cent,  to  10  per  cent,  of  the  normal. 

The  leukocytes  are  often  absolutely  reduced,  but  not  always;  moreover,  a 
neutrophilic  hypoleukocytosis  is  often  found.  [Especially  in  the  remissions 
of  the  disease  when  the  number  of  red  cells  is  rapidly  increasing  and  the  mar- 
row is  very  active. — Ed.] 

The  other  blood  values  differ  little  from  those  of  severe  cases  of  simple 
anemia.  The  hemoglobin  percentage,  the  specific  gravity,  the  amount  of  sol- 
ids, and  the  amount  of  albumin  show  a  diminution  of  their  values  correspond- 
ing with  the  grade  of  the  disease.  [Why  the  authors  do  not  mention  at  this 
point  the  high  color-index,  i.  c,  the  relatively  increased  hemoglobin  which  is 
•so  characteristic  (though  not  invariable)  in  the  disease,  I  do  not  under- 
stand.— Ed.] 

According  to  this,  of  all  the  changes  in  the  blood,  only  the  changes  in  the 
size  of  the  erythrocytes,  and  the  formation  of  the  nuclei  of  the  erythroblasts 
denote  the  variety  of  anemia.  The  appearance  of  megalocytes  and  megalo- 
blasts  is  characteristic  of  progressive  pernicious  anemia,  Avhile  their  permanent 
absence  is  indicative  of  the  simple  form.  For  megaloblasts  and  megalocytes 
appear  in  the  blood  only  when  some  region  of  the  bone-marrow  shows  a  megalo- 
blastic degeneration.  The  simultaneous  occurrence  of  normoblasts,  normo- 
cytes, and  smaller  forms,  as  well  as  a  temporary  predominance  of  one  or  the 
other  of  these  forms,  is  not  at  all  surprising  when  we  consider  that  the  trans- 
formation of  the  bone-marrow  is  always  only  partial,  and  is  often  limited  to 
very  small  areas,  while  in  the  other  regions  of  the  bone-marrow  the  blood  ele- 
ments are  produced  physiologically. 

The  other  properties  of  the  blood  can  only  be  looked  upon  as  denoting  the 
degree  of  the  disease,  as  in  simple  anemia.  We  must  expressly  state  that 
in  undoubted  cases  of  progressive  pernicious  anemia  moderate  values  of  the 
hemoglobin,  a  moderate  number  of  red  blood-corpuscles,  a  moderate  specific 
gravity,  etc.,  may  be  found;  while,  on  the  other  hand,  minimal  values  are  met 
with  in  positive  cases  of  simple  anemia.  It  follows  that  the  degree  of  anemia 
is,  to  a  certain  extent,  independent  of  its  type. 

In  the  clinical  picture  of  progressive  pernicious  anemia  marked  charac- 
teristics are  a  peculiar  pallor  and  a  slight  puffiness  of  the  skin,  which  may 
enable  the  physician  to  guess  the  diagnosis  at  the  first  glance.  No  word  will 
exactly  describe  the  color  of  the  skin;  the  designation  "faded-yellow"  perhaps 
best  portrays  the  real  condition,  but  no  description  can  take  the  place  of  per- 
sonal observation. 

Moderate  jaundice  is  frequently  present,  and  slight  edema  may  be  almost 
always  noticed  in  the  face,  in  the  abdomen,  and  in  the  legs. 

The  contrast  between  the  severity  of  the  constitutional  symptoms  and  the 


PROGRESSIVE  PERNICIOUS  ANEMIA  313 

ur}  I -nourished  appearance  of  the  patient  is  still  more  striking  here  than  in 
chlorosis  and  other  simple  anemias.  There  is  hardly  a  disease  in  which,  with 
so  great  a  cachexia,  the  adipose  tissue  is  so  well  preserved. 

Concerning  the  metabolism  in  progressive  pernicious  anemia  we  have 
little  knowledge.  The  increase  of  proteid  decomposition,  which  has  been 
observed  in  some  case-,  musl  be  due  to  some  inconstant  factor,  for  in  other 
cases  there  is  no  increase  at  all.     The  same  is  true  of  the  oxidation  processes. 

Fever  is  present  in  almost  all  cases,  if  only  transitorily,  but  it  is  by  no 
mean-  characteristic,  and  bears  no  relation  to  the  intensity  of  the  disease.  Its 
origin  is  probably  a  ferment  intoxication  from  the  destruction  of  red  blood- 
COrpUScle-, 

The  cardiac  symptoms  are  prominent.  For  a  long  time  the  disease  was 
considered  to  be  merely  a  symptom  of  severe  cardiac  defeneration.  The  sub- 
jective disturbances  which  are  very  often  troublesome  to  the  patient  consist  of 
(")  palpitation,  brought  about  by  the  least  exertion,  which  often  leads  to  (h) 
true  precordial  distress  and  (c)  severe  dyspnea.  Auscultation  of  the  hear! 
reveals  over  all  the  valve-area-  a  clear,  soft,  usually  systolic,  rarely  diastolic 
murmur.  Percussion  as  a  rule  is  normal.  The  heart  symptoms  are  often  so 
intense  that  during  life  it  is  impossible  to  distinguish  the  condition  from 
genuine  endocarditis. 

Nevertheless,  we  must  state  with  emphasis  that  well-defined  severe  cases 
of  progressive  pernicious  anemia  have  been  observed  in  which  the  heart  showed 
neither  subjective  nor  objective  morbid  phenomena. 

The  weakness  of  the  heart  action  is  best  indicated  by  the  character  of  the 
pulse,  which  usually  is  of  low  ten-ion.  -mall,  and  frequent.  [Very  frequent 
and  very  interesting  in  this  disease  is  the  violent  pulsation  of  the  da-tic 
peripheral  arteries  which  often  equals  that  seen  in  aortic  regurgitation. 
Edwards  '  has  recently  reported  a  case  of  pernicious  anemia  in  which  the 
abdominal  aorta  was  SO  expansile  and  pulsated  so  forcibly  that  aneurism 
seemed  the  only  explanation.     The  carotid-  flap  loosely. —  Ed.] 

On  the  pari  of  the  DIGESTIVE  ORGANS,  marked  anorexia,  persistenl   nausea, 

belching  and  vomiting,  ami  also  unconquerable  repugnance  to  certain  foods, 
for  instance,  meat,  are  often   noticed.     Examination  of  the  gastric  contents 
in  the  living  ha-  not  infrequently  revealed  a  complete  suspension  of  the  gastric 
secretion — " achylia  gastrica"     The  abdomen,  a-  a  rule,  i-  everywhen 
and  not  sensitive  upon  pressure. 

The  motor  capacity  of  the  intestine,  the  power  of  absorption,  ami  the 
i  'on  of  the  intestinal  glands  seem,  a-  a  rule,  normal. 

The  -mi  i;\  i-  generally  normal  or  only  slightly  decreased  in  size,  hut 
there  are  positive  cases  recorded  in  which  extraordinarily  large  splenic  tumor- 
complicated  the  clinical  picture. 

Some  disturbances  of  the  central  nervous  system  may  be  noticed, 
though  in  comparatively  rare  instances.  The  mind  may  be  in  a  condition  of 
deep  depression  <>r  marked  exaltation,  and  the  one  may  repeatedly  alternate 
with  the  other.     Toward  the  end.  disturbances  of  consciousness  and  deep  coma 


i  Trans.  <•/'  //■•    Assn.  <</'  American  Physicians,   1903. 


314  THE  ANEMIAS 

appear.  In  a  number  of  cases,  failure  of  the  memory  and  lasting  impairment 
of  intelligence  have  been  noticed. 

In  the  reports  of  the  last  decade,  numerous  disturbances  of  the  spinal 
cord — in  fact,  a  symptom-complex — have  been  observed  corresponding  exactly 
to  the  picture  of  a  genuine  tabes  dorsalis;  namely,  pupillary  rigidity,  loss  of 
knee-jerks,  ataxia  of  the  limbs,  incontinence  of  the  bladder  and  rectum, 
lancinating  pains,  disturbances  of  sensation,  anesthesia,  and  paresthesia.  In 
some  cases  one  or  another  classical  symptom  of  tabes  is  missing  and  those 
of  the  clinical  counter-picture,  spastic  spinal  paralysis,  are  found.  [Occa- 
sionally intense  neuralgic  pains  in  the  extremities  occur  when  locomotion 
is  attempted.  These  cases  are  doubtless  akin  to  those  of  intermittent  claudi- 
cation.— Ed.] 

It  has  already  been  remarked  that  these  affections  of  the  nervous  system 
are  not  regular  accompaniments  of  progressive  pernicious  anemia;  and  it 
must  be  added  that  in  all  probability  they  are  usually  independent  of  the 
severity  of  the  anemia,  but  due,  as  we  suppose,  to  some  special  etiology.  In 
any'  case,  we  are  not  justified  in  regarding  these  symptoms  as  consequences 
of  the  anemia,  but  they  are  presumably  co-ordinated  consequences  of  the 
same  cause — the  effect  of  toxins.  [Three  groups  of  cases  should  be  here  dis- 
tinguished : 

(a)  Those  in  which  the  nerve  symptoms  appear  late  in  the  course  of  a  case 
of  obvious  pernicious  anemia. 

(b)  Those  in  which  there  are  no  nerve  symptoms  (except  peripheral  pares- 
thesia') «luring  life,  but  obvious  sclerotic  changes  in  the  cord  post  mortem. 

(c)  Those  in  which  the  cord  symptoms  precede  and  overshadow  the  mani- 
festations of  anemia.  This  most  interesting  group  of  cases  has  been  studied 
especially  by  James  J.  Putnam  of  Boston.— Ed.] 

More  exact  clinical  knowledge  of  progressive  pernicious  anemia  has  led 
us  to  give  special  consideration  to  the  changes  in  the  eye,  particularly  to  the 
retinal  hemorrhages  and  their  consequences.  It  cannot  be  denied  that 
these  changes  are  usually  found  in  progressive  pernicious  anemia,  but  isolated 
cases  have  been  met  with  in  which  the  eyes  were  quite  normal ;  and  besides,  in 
undoubted  cases  of  simple  anemia  as  already  mentioned,  profuse  retinal  hemor- 
rhages may  occur.  Consequently  this  symptom  may  be  considered  as  a  sign 
of  the  degree,  and  not  of  the  variety,  of  the  anemia. 

Disorders  of  the  sense  of  hearing  and  of  smell  are  of  slight  importance  and 
exceedingly  uncommon;  but  these  may,  under  some  circumstances,  proceed  to 
complete  suppression  of  these  functions. 

The  post  mortem  findings  in  progressive  pernicious  anemia  are  of  espe- 
cial interest  because  in  some  respects  they  give  important  information  regard- 
ing the  nature  of  the  disease. 

Besides  the  extreme  anemia  of  all  the  organs  and  the  hemorrhages  that 
are  always  present,  though  these  vary  in  amount  and  localization,  siderosis 
is  always  found,  that  is,  an  abnormally  increased  amount  of  iron  in  the  inter- 
nal organs,  especially  in  the  liver,  in  the  spleen,  in  the  bone-marrow,  and  in 
the  lymph-glands.  [Neither  the  hemorrhage  nor  the  siderosis  is  invariable, 
though  in  the  majority  of  cases  they  are  found. — Ed.]     This  increase  of  iron 


PROGRESSIVE  PERNICIOUS  ANEMIA  315 

in  progressive  pernicious  anemia  may  be  considered  a  proof  of  the  invariably 
concomitant  increased  destruction  of  red  corpuscles. 

Fatty  degeneration,  the  clinical  consequences  of  which  have  already 
been  alluded  to,  is  found  quite  often  in  the  muscles  of  the  extremities,  of  the 
trunk,  and  conspicuously  in  the  muscles  of  the  eye.  Almost  always  we  find 
the  fatty  degeneration  of  the  heart  muscle  which  is  such  a  well-known  charac- 
teristic of  the  disease.  The  fatty  degeneration  of  the  arteriole-  ami  capillaries 
is  interesting  because  it  occasions  hemorrhages  in  the  internal  organs. 

Attention  must  be  devoted  to  the  digestive  tract,  because  the  achylia 
gastrica  sometime-  presenl  leads  us  to  expect  definite  anatomical  changes.  In 
fad  a  more  or  less  marked  atrophy  of  the  gastric  and  intestinal  gland-  has 
been  found  repeatedly,  yet  the  pathologico-anatomical  changes  at  the  autopsy 
by  no  mean-  always  coincide  with  the  symptoms  during  life;  quite  marked 
degenerative  changes  have  been  found  in  cases  where  the  functions  of  the 
Btomach  and  intestine-  had  apparently  been  perfectly  normal,  while,  on  the 
other  hand,  in  cases  in  which  achylia  gastrica  undoubtedly  had  been  presenl 
no  anatomical   changes  were  found.     The  relations  of  the  gastro-intestinal 

atrophy  to   progressive  pernicious  anemia  have  not  as  ye\    1 n   sufficiently 

demonstrated.  It  must  be  remembered  that  only  comparatively  few  cases  of 
anemia,  and  those  not  always  the  most  severe,  show  these  changes:  and  fur- 
thermore, that  in  a  -eric-  of  other  changes  nowise  related  to  progressive  per- 
nicious anemia,  atrophy  of  the  gastro-intestinal  gland-  has  been  found.  The 
supposition  i-  reasonable  that  this  atrophy  and  anemia  have  no  causal  relation 
to  each  other,  hut  that  they  represent  the  effects  of  a  common  cau-e. 

A  U-w  instances  of  progressive  pernicious  anemia  have  been  reported  in 
which  carcinoma  <>f  the  stomach,  in  extent  about  the  size  of  a  hazel-nut,  and 
without  ulceration  or  metastases,  has  been  found.  The  -mall  size  of  these 
tumor-  prevents  our  recognizing  in  them  the  cau-e  of  the  anemia:  hut  if  one 
i-  not  content  tu  call  it  ••coincidence*'  the  supposition  that  progressive  per- 
niciou-  anemia  has  prepared  the  way  for  the  formation  of  the  tumor-  is  uol 
altogether  unreasonable.  Of  course,  the  cases  in  which  advanced  carcinosis  is 
found  combined  with  progressive  pernicious  anemia  must  be  judged  quite  dif- 
ferently ;  here  it  i-  probable  that  the  carcinoma  i-  the  cau-e  of  the  anemia. 

on  account  of  the  symptoms  suggesting  tabes  ami  other  diseases  the  cen- 
tral nervous  system  ha-  been  made  the  subjeel  of  especially  thorough  re- 
searches. Besides  the  hemorrhages  which  are  most  apt  to  occur  in  the  brain 
ami  spinal  i-ord.  we  lind  focal  and  also  diffuse  degeneration-  of  the  nerve 
fibers  in  the  white  substance  of  the  Bpinal  cord,  with  consecutive  prolif- 
eration of  the  connective  tissue.  These  changes,  which  occur  particularly  in 
the  posterior  columns,  are  without  doubt  the  cause  of  the  severe  clinical 
symptoms. 

The  changes  in  the  bone-marrow,  especially  those  revealed  by  Ihr  micro- 
scopical  examination  of  Ihr  organ,  are  the  most  important  of  all.  because  we 
lind  in  them  convincing  proof  of  the  aecessity  of  classifying  anemic  conditions 
according  to  the  mode  of  blood-regeneration.  If  we  consider  only  the  macro- 
scopical   evidences,   the  classification   of  anemia   appears   impossible;  for   in 

alino-t   all   ea-e-  \\e   lind  a   trail-formation   of  the  yellow    fat    marrow    into   red 


316  THE  ANEMIAS 

lymphoid  marrow,  these  changes  including  sometimes  smaller,  sometimes 
larger,  portions  of  the  bone-marrow.  If,  in  a  case  of  simple  anemia,  we  were 
to  examine  such  a  portion  microscopically,  an  exact  picture  of  the  normal 
lymphoid  marrow  would  be  seen,  such  as  is  always  found  in  the  ribs,  the  verte- 
bra, the  sternum,  and  is  besides  characterized  by  the  presence  of  white  cells 
(which  we  do  not  take  into  consideration),  and  by  red  blood-corpuscles  of  the 
same  size  as  the  erythrocytes  of  normal  blood,  some  without,  some  with,  nuclei. 
But  the  picture  we  obtain  in  cases  of  progressive  pernicious  anemia  of  all, 
or  of  many,  of  these  transformed  red  bone-marrow  regions  is  entirely  differ- 
ent. The  nucleated,  as  well  as  the  non-nucleated,  red  blood-corpuscles  are  of 
such  a  size,  and  contain  such  a  rich  quantity  of  hemoglobin,  as  is  never  ob- 
served in  the  bone-marrow  of  the  normal  adult  but  only  in  the  embryo.  These 
differences  seem  to  be  so  essential  as  to  necessitate  a  special  classification  of  the 
anemias,  even  if  they  did  not  bear  out  what  we  should  expect  from  the  clinical 
symptoms  and  the  condition  of  the  blood. 

In  progressive  pernicious  anemia  the  whole  fat  marrow  very  rarely  degen- 
erates into  lymphoid  megaloblastic  marrow,  and  this  is  a  factor  which  enables 
us  the  better  to  comprehend  certain  variations  in  the  blood  findings,  and  is  of 
the  greatest  importance  in  practical  diagnosis.  Often  only  a  portion  of  the 
lymphoid  marrow  shows  a  megaloblastic  structure,  while  the  other  regions  are 
lympho-normoblastic.  Moreover,  only  a  part  of  the  fat  marrow  is  diseased 
in  most  cases.  Of  course,  the  number  of  megaloblasts  and  megalocytes  con- 
tained in  the  circulating  blood  depends  upon  the  size  of  the  megaloblastic  por- 
tion of  the  bone-marrow,  and  other  temporary  variations  in  the  composition 
of  the  blood  may  be  thus  explained. 

It  is  our  purpose  to  discuss  in  this  article  only  points  of  practical  impor- 
tance. But  we  must  not  forget  that  a  series  of  questions  most  intimately 
related  to  the  changes  in  the  bone-marrow  are  still  awaiting  solution.  For 
bothriocephahis  anemia,  the  correct  explanation  has  probably  been  given,  and 
most  authors  of  the  present  day  maintain  the  view  that  the  toxin  of  the  bothrio- 
cephalus  causes  the  specific  megaloblastic  changes  of  the  bone-marrow.  This 
gives  us  a  hint  as  to  the  etiology  of  other  types  of  progressive  pernicious  ane- 
mia, and  inclines  us  to  the  general  supposition  of  a  specific  toxic  influence. 
It  is  more  difficult  to  answer  the  question  as  to  what  particular  circumstances 
transform  a  simple  anemia  into  the  megaloblastic  form,  an  occurrence  which 
must  certainly  be  considered  infrequent  considering  the  prevalence  of  simple 
anemia.  At  present,  the  toxin  hypothesis  does  not  sufficiently  explain  the 
extraordinarily  rare  cases  in  which  progressive  pernicious  anemia  develops  as 
the  consequence  of  a  simple  posthemorrhagic  anemia. 

But  it  cannot  lie  disputed  that  progressive  pernicious  anemia  may  develop 
from  a  simple  anemia,  and  this  confirms  the  view  that  there  must  be  transi- 
tional stages  in  which  it  is  exceedingly  difficult,  and  often  even  impossible,  to 
determine  to  which  class  of  anemias  a  given  case  belongs.  Still,  we  meet  with 
such  transitions  and  intermediate  stages  within  the  whole  domain  of  pathol- 
ogy, in  fact  in  all  departments  of  natural  science;  they  must  not,  therefore, 
be  an  obstacle  to  the  differentiation  of  the  fully  developed  forms,  nor  are  they 
proofs  of  the  non-existence  of  special  types  of  the  disease. 


PROGRESSIVE   PERNICIOUS  ANEMIA  317 

Therefore,  in  spite  of  many  uncertainties,  we  are  warranted  in  stating  that 
the  condition  which  most  distinctively  stamps  progressive  pernicious  anemia 
may  be  described  as  follows:  Pbogressivb  pernicious  anemia  [s  not  a\  EX- 
TREMELY MARKED  DEGREE  OF  ANEMIA,  BIT  A  DISTINCTIVE  TYPE  OF  THE  DISEASE 
CHARACTERIZED   BY    A    PECULIAR    MODE    OF    BLOOD-FORMATION. 

THE   COURSE   OF  THE  DISEASE 

The  course  of  progressive  pernicious  anemia  presents  some  remarkable  and 
characteristic  features,  which  are  more  pronounced  than  in  any  other  disease. 
Only  occasionally  does  the  disease  run  a  continuously  progressive  and  fatal 
course;  usually  the  morbid  condition  is  relieved  once  or  several  times  by  a 
state  lasting  for  weeks  or  months  that  may  simulate  almost  perfed  bealth. 
These  "  remissions  "  often  follow  stages  of  the  disease  so  severe  that  they  seem 
to  be  the  Immediate  precursors  of  death;  during  extreme  prostration,  a  change 
suddenly  sets  in — spontaneously  or  under  the  influence  of  medication — a 
change  thai  within  a  few  week-  often  Leads  to  apparently  perfed  recovery. 
Remissions  such  as  these,  as  many  as  five  or  more,  have  repeatedly  been  noticed 
in  the  same  individual. 

The  duration  of  the  disease  varies  from  a  few  weeks  to  five  or  ten  years; 
but  by  far  the  majority  of  patient-  succumb  in  a  year  or  a  year  and  a  half 
after  the  symptoms  have  distinctly  developed. 

The  prognosis  of  the  disease  is  exceedingly  grave;  the  so-called  recoveries 
have  probably  been  only  the  beginning  of  the  remissions,  which  delay,  but 
cannot  avert,  the  fatal  issue.  According  to  our  presenl  knowledge,  the  disease 
must  he  considered  incurable  and  fatal.  |  In  the  va-t  majority  of  cases,  in- 
cluding most  of  those  published  a-  "cures/'  death  follow-  within  three  year-, 
but  there  are  a  (^w  well-authenticated  cases  -till  alive  ;tt  the  end  of  ten  years. 
Perhaps  1  in  100  may  recover. — Ed.] 

Bothriocephalic  anemia  is  a  striking  exception  to  this  rule.  This  form  of 
the  affection  is  often  entirely  cured  by  the  expulsion  of  the  worm,  even  though 
Bymptoms  of  progressive  pernicious  anemia  have  already  developed  to  the  full- 
esl  extent,  and  the  anemia  has  attained  a  high  degree.  We  recognize  from 
this  that  the  mere  presence  in  the  blood  of  megaloblasts  and  megalocytes  -i.  e., 
the  megaloblastic  degeneration  of  the  bone-marrow— does  not  in  itself  make 
the  prognosis  absolutely  unfavorable,  hut  that  even  with  this  the  disease  may 
Lose  it-  progressive  character  if  we  can  succeed  in  removing  its  cause  from  the 
organism.  So  long  a-  we  are  ignorant  of  the  origin  of  progressive  pernicious 
anemia,  so  long  are  the  prospects  of  a  cure  decidedly  unfavorable. 

The  mo-!  important  point  in  the  diagnosis  i-  the  differentiation  between 
simple  and  progressive  pernicious  anemia.  In  well-marked  cases  of  the  latter, 
the  general  clinical  picture  enable-  as  to  make  the  diagnosis.  The  peculiar 
pallor,  the  extreme  weakness,  the  tired  expression,  the  marked  development 
of  hear!  symptoms,  the  retinal  hemorrhages,  the  striking  contrast  between  the 
asthenia  and  the  well-preserved  adipose  tissue  all  these  combine  to  form  a 
picture  that  clearly  .-tamp-  the  disease  alter  a  merely  superficial  examination. 


318  THE  ANEMIAS 

If  the  patient  is  under  observation  for  a  longer  time,  the  appearance  of  a 
remission  is  a  remarkable  aid  to  the  diagnosis.  Even  in  such  characteristic 
cases,  besides  the  clinical  examination,  we  must  not  omit  an  examination  of 
the  blood  as  a  control  test ;  if  the  general  clinical  picture  of  the  disease  is  not 
perfectly  developed,  blood  examination  is  even  more  essential. 

If  we  find  in  the  blood  undoubted  megaloblasts  besides  genuine  megalocytes, 
the  diagnosis  of  progressive  pernicious  anemia  is  established  beyond  doubt. 
[This  statement  is  certainly  too  strong.  Undoubted  megaloblasts  with  a 
majority  of  normoblasts  occur  in  some  perfectly  curable  post-malarial  anemias. 
It  is  the  predominance,  not  the  presence,  of  megaloblasts  and  megalocytes 
that  is  most  significant. — Ed.]  If  we  do  not  find  them  it  is  more  difficult 
to  reach  a  conclusion.  Whoever  is  careful  to  bear  in  mind  the  above-mentioned 
changes  in  the  bone-marrow  will  exclude  pernicious  anemia  in  doubtful  cases 
only  after  repeated  examinations  of  the  blood  have  shown  it  to  be  entirely 
free  from  these  characteristic  elements. 

We  must  always  remember  that  the  megaloblasts  usually  pass  only  in  small 
numbers  from  the  bone-marrow  into  the  blood.  Hence  we  must  examine 
thoroughly  several  technically  perfect  preparations  before  we  can  positively 
say  that  this  variety  of  cell  is  absent.  If  the  blood  is  of  a  pronounced  megalo- 
cytic  character,  then  the  diagnosis  of  progressive  pernicious  anemia  may  be 
made  even  though  megaloblasts  are  absent,  because  the  appearance  in  the  blood 
of  large  numbers  of  megalocytes  cannot  occur  without  a  previous  megaloblastic 
transformation  of  the  bone-marrow. 

Another  diagnostic  difficulty  is  the  fact  that  there  are  undoubtedly  cell 
forms  which  morphologically  represent  a  transitional  stage  between  normo- 
blasts and  megaloblasts.  If  these  are  sparse,  they  may  be  left  entirely  out  of 
consideration;  if  they  appear  in  great  numbers,  they  are  indicative  of  pro- 
gressive pernicious  anemia. 

To  determine  the  cause  of  progressive  pernicious  anemia,  an  examination 
of  the  feces  for  tape-worm  ova  is  necessarily  important;  the  presence  of  the 
bothriocephalus  ova  or  links  will  aid  materially  in  the  prognosis  and  treat- 
ment. [Uncinaria  eggs  should  also  be  looked  for,  though  the  type  of  anemia 
produced  by  uncinariasis  is  usually  somewhat  different  from  that  described 
here. — Ed.] 

From  the  standpoint  of  differential  diagnosis  we  must  bear  in  mind  endo- 
carditis, carcinoma  of  the  gastro-intestinal  tract,  tabes  dorsalis,  and  Addi- 
son's disease,  and,  during  the  comatose  terminal  stages  of  the  malady,  other 
affections  in  the  course  of  which  severe  disturbances  of  consciousness  occur. 
In  these  cases,  the  verdict  depends  mainly  upon  the  blood  examination. 

THERAPY 

Treatment  offers  hope  of  success  only  in  the  bothriocephalus  anemia. 
After  the  anthelmintic  (extr.  filix  mas)  has  produced  its  effect,  if  the  anemia 
is  not  too  far  advanced  a  definite  cure  will  shortly  follow.  These  results 
encourage  us  to  try  the  filix  mas  even  in  cases  in  which  the  bothriocephalus 
has  not  been  found. 


THERAPY  319 

Marked  improvement  and  even  apparent  cure  has  been  repeatedly  noticed 
after  the  stomach  and  intestines  had  heen  thoroughly  cleansed  by  laxatives 
and  irrigations.  In  such  cases  we  are  warranted  in  the  interpretation  of  the 
progressive  pernicious  anemia  as  an  autointoxication  from  the  gastro-intestinal 
tract. 

Organotherapy,  the  treatment  of  the  disease  with  bone-marrow,  has  thus 
far  given  no  results. 

On  the  contrary,  some  very  surprising,  though  not  always  accountable, 
results  have  been  attained  by  the  transfusion  of  small  quantities  (40-100 
c.c.)  of  defibrinated  human  blood.  In  several  cases  transfusion  has  been 
followed  immediately  by  the  onset  of  a  complete  remission  of  the  disease  and 
life  was  prolonged  for  months,  though  when  transfusion  was  again  performed, 
after  a  relapse,  it  was  ineffectual.  But  if  the  patient's  life  is  endangered, 
and  if  coma  has  already  -et  in.  this  operation  is  our  last  hope  and  resource, 
and  should  at  least  be  attempted. 

The  most  important  and  successful  treatment  is  by  arsenic.  To  this 
remedy  we  are  indebted  for  an  extraordinarily  large  number  of  apparent  cures, 
and  by  its  aid  in  some  cases  we  succeed  in  bringing  about  remissions  and  in 
delaying  the  imminent  outbreak  of  a  relapse. 

Nevertheless  there  can  be  no  lasting  cure,  even  with  the  aid  of  arsenic. 

Tin-  remedy  i-  administered  according  to  the  generally  observed  rules: 
Small  doses  in  the  beginning  and  gradually  increased,  Long-continued  use, 
and  a  gradual  decrease.  The  doses  should  be  adapted  to  the  individual  sus- 
ceptibility and  reaction;  as  a  rule,  even  during  the  acme  of  the  treatment, 
we  lind  doses  -mailer  than  the  maximal  to  be  sufficient.  During  the  remission, 
when  no  Bymptoms  are  present,  it  is  well  to  give  the  remedy  from  time  to 
time  for  several  weeks.  The  best  indication  for  a  renewal  of  the  treatment 
is  afforded  by  regular  examination-  of  the  blood,  which  may  give  warning 
a  new  outbreak  before  the  clinical  symptoms  suggest   it. 

An  unfortunate  idiosyncrasy  for  arsenic  not  infrequently  develop-  in  the 
course  of  treatment,  and  may  prove  disastrous  for  the  patient,  inasmuch  a-  the 
proposed  substitutes  for  tin-  remedy  have  not  yet  borne  the  tesl  of  experience. 

A-  for  general  treatment,  resl  and  comfort  are  of  paramount  importance. 
The  diet  must  be  adapted  to  th«'  individual  susceptibility  of  the  stomach  and 
intestine,  as  well  a-  to  the  sometimes  insurmountable  repugnance  of  the 
patient  for  meat.  In  view  of  the  debility  of  the  patient,  hydrotherapeutic 
treatment  i~  not  advisable,  hut  sponge  hath-  may  be  given  without  danger. 
General  massage  i-  preferable  to  bathing.  A  change  of  climate  may  be  indi- 
cated during  th-'  remissions,  and  a  sojourn  in  a  mountainous  region  of  mod- 
erate altitude  is  more  Likely  to  prove  beneficial  than  any  other  climatic  change. 

LITEB  LTTTRE 

The  earlier  literature  of  this  subject,  in  .-ill  it-  details,  is  irix'-n  by  Ehrlich-Lazarus, 
"Anemia,""  Nothnagel^  Handbuch,"  viii,  Wien,  L900.  More  comprehensive  works 
which  have  appeared  are:  Strauss  and  Rohnstein,  "The  Composition  of  the  Blood  in 
Different  Anemias,"  Berlin,  1901 ;  Schaumann,  "Pernicious  Anemia  in  the  Light  of 
the  Modern  Toxin  Hypothesis,"  Volkmann's  Clinical  Lecturt  .  New  Series,  No.  l's7. 


CHLOROSIS 

By    E.    GRAWITZ,    Charlottenburg    (Berlin) 

Among  the  numerous  cases  of  anemia  constantly  coming  under  observa- 
tion in  the  hospital,  one  group  stands  out  prominently,  which,  in  regard  to  the 
origin  as  well  as  the  symptomatology,  and  the  entire  course  of  the  affection, 
occupies  a  distinctive  position,  and,  since  the  time  of  Hippocrates,  has  been 
considered  to  indicate  an  impoverished  condition  of  the  blood.  [As  Stengel 
has  recently  remarked,  there  seem  to  be  fewer  cases  diagnosticated  as  chlorosis 
in  the  clinics  of  the  larger  American  cities  than  was  the  case  some  years  ago. 
Whether  there  are,  in  fact,  fewer  cases  or  whether  better  technic  makes  us 
reject  many  that  were  supposedly,  but  not  actually,  chlorotic,  I  do  not 
know. — Ed.] 

SYMPTOMS 

This  group  consists  almost  exclusively  of  young  girls  and  young  women, 
in  whom  the  anemia  betrays  itself  by  a  conspicuous  pallor  of  the  skin  and  the 
mucous  membrane.  [I  have  never  seen  in  adolescent  boys  any  cases  of  anemia 
at  all  resembling  those  which  in  girls  we  call  chlorosis,  and  those  reported  in 
literature  are  mostly  a  good  many  years  back  and  vaguely  reported. — Ed.] 
In  many  cases  there  is  also  a  decided  yellowish  tinge  which  may  sometimes 
verge  upon  green,  and,  as  frequently  happens  in  pathology,  from  this  by  no 
means  significant  nor  even  very  frequent  green  color,  a  term  has  originated 
which  has  long  encompassed  the  entire  symptom-complex,  and  has  become 
current  in  the  language  of  all  countries;  namely,  the  designation  "chlorosis" 
(from  x^°P°s>  greenish). 

Besides  this  pale  or  pale  yellow  discoloration  of  the  skin,  there  are  in 
many  cases  dark  gray  rings  around  the  eyes;  it  is  especially  worthy  of  note 
that  there  is  no  sign  of  loss  of  the  subcutaneous  adipose  tissue;  on  the  con- 
trary, many  of  these  patients  have  a  plentiful  layer  of  fat. 

It  may  be  seen,  therefore,  that  this  form  of  anemia  is  not  due  to  a  general 
cachexia,  but  occurs  in  well-nourished  persons,  a  fact  which  is  confirmed  by 
an  examination  of  other  organs. 

Besides  the  peculiar  color  of  the  skin,  the  majority  of  chlorotics  show  a 
more  or  less  pronounced  edematous  infiltration  of  this  tissue,  so  that,  for 
instance,  the  lower  eyelids  often  seem  swollen,  and  imprints  of  the  examining 
fingers  on  the  back  and  at  the  ankles  of  the  patient  are  distinctly  persistent. 

These  signs  lend  to  the  patient  a  peculiar  doughy  appearance,  which,  at 
320 


SYMPTOMS  321 

the  first  glance,  vividly  recalls  that  of  persons  affected  with  acute  nephritis, 
yel  this,  of  course,  is  not  due  to  the  yellowish  discoloration. 

The  circulatory  apparatus  presents  numerous  and  striking  symptoms.  In 
the  heart  there  is  almost  always  an  increase  of  the  area  of  dulness,  to  the  righl 
and  to  the  left.  The  hand  may  feel  a  distinct  systolic  thrill,  especially  over 
the  pulmonary  artery,  and  on  auscultation  systolic  murmurs,  which  commonly 
have  a  peculiar  blowing  character,  are  very  distinctly  heard. 

These  cardiac  murmurs  have  been  recognized  for  a  long  time.  and.  in  spite 
of  careful  study,  are  still  subjects  of  dispute.  The  murmurs  are  usually  loud- 
est over  the  pulmonary  artery,  and  an  attempt  has  heen  made  to  explain  them 
by  the  fact  that  there  is  a  relaxation  of  the  heart  muscle  owing  to  insufficiency 
of  the  blood-supply,  that  the  papillary  muscles  do  not  contrad  with  sufficient 
power,  that,  therefore,  during  systole  there  is  a  relative  insufficiency  of  Ihr 
auriculoventricular  ruins  which  causes  a  regurgitation  of  the  hlood  to  the 
auricles  during  systole  in  the  same  manner  as  in  cases  of  organic  mitral  insuf- 
ficiency. 

This  much  is  certain:  that  these  systolic  murmurs  are  intimately  related 
with  the  anemic  condition  of  the  hlood.  that  they  appear  when  the  disease 
develops,  and  disappear  when  the  general  clinical  picture  shows  improvement. 

Therefore,  they  have  been  properly  called  "anemic  murmurs."  in  contra- 
distinction to  heart  murmurs  produced  by  valvular  lesions  which  are  desig- 
nated "organic  murmurs."  and  an  exact  knowledge  of  these  conditions  is  the 
more  important  as  it  is  frequently  the  duty  of  the  physician  to  decide  whether 
changes  and  murmurs  in  the  heart,  especially  in  young  persons,  are  to  be 
attributed  to  a  valvular  Lesion  or  whether  they  are  only  accompanying  symp- 
toms of  anemia.  [The  term,  u anemic "  or  "hemic"'  murmurs,  is  not  well 
chosen,  for  the  majority  of  such  murmurs  occur  not  in  anemic  cases  hut  in 
fevers,  in  neurotic  or  excited  conditions,  in  growing  children  and  after  any 
violent  exertion  (boat-races,  etc.).  On  the  other  hand,  cases  of  marked 
anemia  without  any  murmurs  are  not  very  uncommon.  1  prefer  the  term 
"  functional  murmur." — Ed.]  As  an  instance  of  the  importance  of  this  dif- 
ferential-diagnostic distinction,  we  may  mention  the  requirements  for  enlist- 
ment  in  military  service,  in  which  this  question  is  of  momentous  importance. 

As  a  criterion  in  practice  the  following  important  point-  favor  anemic 
murmurs: 

1.  The  existence  of  distinct   anemia. 

2.  The  simultaneous  presence  of  the  systolic  murmur  over  all  the  valves. 

3.  Especial  Loudness  in  the  pulmonary  area. 

I.  Absence  of  that  accentuation  of  the  pulmonic  second  sound  which  con- 
stantly accompanies  insufficiency  of  the  mitral  valve. 

It  must,  however,  be  stated  with  emphasis  that  simple  as  this  appear-  in 
theory  it  Is  often  difficult  in  practice  to  arrive  at  a  decision;  for,  in  the  first 
place,  training  i-  accessary  to  make  these  examination-  correctly,  and,  further, 
prolonged  observation  of  the  patient  is  the  only  decisive  criterion,  for,  as  has 
heen  -tateii.  anemic  murmur-  are  transitory  while  organic  heart  murmurs  are 
permanent. 

Neither  doe-  the  character  of  the  pulse  give  reliable  information  in  regard 


322  CHLOROSIS 

to  this  question.  The  pulse  of  anemics  is  for  the  most  part  simply  accelerated, 
of  varying  strength,  and  often  slightly  dicrotic;  in  some  cases  a  crural  mur, 
mur  has  been  noted.  Obviously,  then,  the  pulse  of  chlorotics  presents  no  char- 
acteristic changes. 

The  acceleration  of  the  heart  heat  and  of  the  pulse  is  explained  by  a  diminu- 
tion of  hemoglobin,  as  the  blood,  in  order  to  accomplish  the  required  oxida- 
tion of  the  whole  organism,  must  circulate  more  rapidly  than  when  it  contains 
a  normal  amount  of  hemoglobin.  As  a  result  of  this,  acceleration  of  the  heart's 
action  is  one  of  the  common  symptoms  of  chlorosis  as  well  as  of  other  forms 
of  anemia. 

Subjectively,  the  patients  are  often  vividly  conscious  of  this  acceleration, 
so  that  a  troublesome  sensation  of  cardiac  palpitation  develops,  a  point  which 
has  been  noted  in  the  earliest  literature  as  a  prominent  symptom  of  chlorosis. 
This  sensation  becomes  aggravated  upon  exertion  as  when  they  attend  to  their 
housework,  ascend  stairs,  etc.  As  a  result  they  readil}''  become  short  of  breath, 
and  the  rapid  beating  of  the  heart  which  appears  after  these  slight  exertions 
often  persists  afterward  as  a  subjective  but  very  disagreeable  symptom. 

In  these  cases  it  is  surprising  to  note  that  some  chlorotics,  who  during  the 
day  become  dyspneic  on  the  slightest  exertion,  are  able  in  the  evening  to 
attend  a  ball  and  indulge  most  immoderately  in  dancing,  and  even  to  con- 
tinue this  exercise  for  hours  without  any  difficulty  in  breathing  approaching 
that  which  occurs  during  the  day,  when,  for  instance,  they  ascend  only  one 
flight  of  stairs.  Of  course,  upon  the  following  morning,  a  particularly  great 
prostration  is  discernible. 

Similar  to  the  murmurs  in  the  heart,  in  such  patients  "  venous  murmurs  " 
have  for  a  long  time  been  recognized  which  are  designated  "  nuns  murmurs  " 
or  also  "  bruit  de  diable."  These  are  best  auscultated  over  the  sterno-clavicu- 
lar  articulation;  care  must,  however,  be  exercised  that  the  neck  of  the  person 
is  not  turned  too  much  to  one  side,  for,  in  this  case,  the  murmur  may  also  be 
noted  in  normal  subjects.  This  murmur  is  due  to  the  circumstance  that  the 
jugular  vein  is  held  by  tense  bands  situated  behind  the  articulation  just  men- 
tioned, so  that  in  this  region  it  cannot  expand  and  contract  with  facility,  as 
it  does,  for  instance,  higher  up  in  the  neck.  Now,  since  in  anemics  the  lumen 
of  the  vein  is  lessened — being  less  full — when  the  blood  enters  from  the  nar- 
rowed portions  into  the  easily  dilatable  parts  previously  mentioned,  differences 
in  the  blood  current  arise  which  give  rise  to  these  murmurs.  This  is  the  usual 
explanation  of  these  conspicuous  venous  murmurs,  but  it  is  unsatisfactory, 
inasmuch  as  in  other  anemic  conditions  in  which  the  blood  reveals  much 
greater  deterioration  than  in  chlorosis — therefore  a  more  favorable  condition 
for  the  production  of  the  murmurs — no  adventitious  bruits  are  discernible. 
[It  should  be  mentioned  at  this  point  that  violent  pulsations  of  the  peripheral 
arteries,  especially  the  carotids,  are  noticeable  and  sometimes  troublesome  in 
cases  of  severe  anemia  of  any  type.  The  arteries  flap  and  jump  so  violently 
as  to  remind  one  of  the  conditions  seen  in  aortic  regurgitation. 

Dilatation  of  the  heart  is  not  uncommon  and  may  be  demonstrated  by 
radioscopy  or  by  percussion.  A  beautiful  picture  of  a  heart  dilated  in  the 
course  of  a  case  of  chlorosis  is  included  in  the  v.  Ziemssen-Rieder  Atlas. — Ed.] 


SYMPTOMS  323 

The  respiratory  apparatus  in  chlorotic-  shows  few  deviations  from  the 
normal.  A  symptom  noticeable  in  many  of  the  patients  is  an  accelerated  res- 
piration rule,  which  is  to  be  explained,  like  the  acceleration  of  the  heart's 
action,  by  a  relative  deficiency  of  the  blood  in  oxygen.  This,  however,  is  nol 
characteristic  of  chlorosis,  lud  is  also  met  with  in  other  affections  accompanied 
by  deficiency  in  hemoglobin. 

Much  more  numerous  are  the  symptoms  on  the  part  of  the  digestive  appa- 
ratus. First  of  all.  as  an  almost  invariable  symptom,  there  is  found  anorexia 
and  repugnance  for  certain  kinds  of  food,  for  instance,  meat;  and.  on  the 
other  hand,  and  this  is  a  characteristic  symptom  of  the  disease,  a  morbid  desire 
for  food  difficult  to  digest  or  wholly  indigestible.  Thus,  many  of  these  patients 
have  an  especial  liking  for  sour  foods,  vinegar,  pickled  products,  etc.,  and 
furthermore,  for  lime,  chalk,  slate  pencil-  and  the  like:  longings  which  remind 
one  forcibly  of  similar  cravings  in  pregnancy. 

Aionv  of  the  muscular  wall  of  the  stomach  is  often  found,  which  not  infre- 
quently leads  to  dilatation  and  displacements  of  this  organ.  Still,  T  cannot 
coincide  in  the  opinion  of  Meinert,  who  considers  gastroptosis,  that  is.  the 
pathological  descent  of  the  fundus  of  the  stomach,  a  constant  symptom  of 
chlorosis,  and  even  makes  it  responsible  for  the  origin  of  the  whole  disease. 

As  a  matter  of  fact,  there  i>  often  found  in  young  girls  a  displacement  of 
the  stomach  from  its  norma]  limits,  the  result  of  tight  lacing  and  the  wearing 
of  corsets;  and.  as  general  weakness  of  the  muscles  exists  on  account  of  the 
anemia,  conditions  are  very  favorable  for  the  development  of  gastroptosis  and 
dilatation  in  consequence  of  the  stagnation  of  food  and  tight  lacing. 

In  many  cases  ///'•  secretory  activity  of  tin-  stomach  is  quite  normal;  in 
others  an  excessive  production  of  hydrochloric  acid  is  met  with:  and  in  still 
others  acidity  is  decreased.  These,  however,  are  fads  that  musl  he  ascer- 
tained by  direct  examination  of  tin1  ga&tric  contents,  and  should  never  he 
guessed  at  from  the  subjective  complaint-,  a-,  for  instance,  from  the  inclina- 
tion to  cat  chalk. 

The  activity   of  tin-   intestines   is   usually   disturbed,   and    constipation    is 

one    of    the    COmmOnesI     Symptoms;     indeed,     as     will     he    seen     later,     theories 

have  been  developed  which  ascribe  the  origin  of  the  whole  disease  to  this 

phen< non. 

Concerning  the  metabolism  of  chlorotics,  exact  researches  have  been  made. 
especially  by  v.  Nfoorden  and  his  pupils,  from  which  ii  is  ascertained  that  in 
these  patients  no  especially  increased  waste  of  albumin  occurs,  that  the  absorp- 
tion of  oxygen  is  within  normal  limit-,  and  that  the  excretion  of  urea  -hows 
no  noteworthy  change. 

Tin'  body  tan i><ral nrc  i-  neither  increased  nor  diminished.  'The  appear- 
ance of  fever  is  probably  to  be  explained  lor  the  mo-t  part  by  the  presence  of 
complications.  Slight  transitory  rises  of  temperature  without  demonstrable 
organic  changes  occur  in  Bome  cases;  but  «v  musl  consider  the  close  relation- 
ship between  chlorosis  and  hysteria  a  fact  which  we  shall  consider  frequently 
lateT  ()11 — jn  which   fever  of  like  character  also  IS  noted,  and  ha-  thus   far  not 

been  satisfactorily  explained. 

In  chlorotics  the  sexual  functions  are  disturbed  in  various  ways:  and  here 


324  CHLOROSIS 

again  the  attempt  has  been  made  to  refer  the  development  of  the  disease  to 
these  disturbances. 

Menstruation  in  chlorotic  girls  is  delayed,  or  if  it  has  already  appeared  it 
becomes  scanty  or  ceases  when  the  chlorosis  develops.  In  contrast  to  this,  other 
chlorotics  suffer  from  remarkably  profuse  menstruation,  which  sometimes  may 
be  normal  for  a  few  months ;  at  the  same  time,  there  is  considerable  suffering 
at  the  onset,  such  as  headache,  general  nausea,  indisposition,  pain  in  the  abdo- 
men, etc. 

In  opposition,  however,  to  the  opinion  that  the  menstrual  anomalies  are 
the  actual  cause  of  the  disease,  it  must  be  maintained  that  many  chlorotics 
menstruate  in  a  perfectly  normal  manner  until  the  onset  of  the  disease,  so 
that,  logically,  these  anomalies  which  develop  during  the  course  of  the  chloro- 
sis must  undoubtedly  be  considered  as  secondary  conditions.  Leukorrhea  is 
also  very  frequent  in  chlorotics. 

The  symptoms  referable  to  the  nervous  system  are  numerous,  and  here 
we  must  differentiate  two  groups,  one  of  which  may  be  easily  recognized  as 
solely  a  consequence  of  the  anemic  condition  of  the  blood,  while  the  other  has 
an  independent  character  and  is  specially  significant.  To  the  first  group  belong 
vertigo,  specks  before  the  eyes,  syncope,  which  can  be  easily  explained  as  due 
to  a  deficient  supply  of  blood  to  the  brain,  all  the  more  so  as  the  symptoms 
ameliorate  when  the  patients  are  kept  in  a  recumbent  posture,  so  that  the 
access  of  blood  to  the  brain  is  facilitated,  while  they  become  most  prominent 
as  soon  as  the  patients  assume  the  erect  position  or  attempt  to  walk.  These 
symptoms  of  anemia  of  the  brain,  resulting  from  unsatisfactory  circulation 
of  the  blood — at  the  same  time  poor  in  oxygen — become  manifest  in  a  similar 
manner  also  in  other  forms  of  anemia. 

In  flic  second  group  (nervous  symptoms  independent  of  anemia)  belong 
especially  psychical  anomalies,  which  manifest  themselves  by  a  change  in  the 
disposition,  and  a  dislike  for  mental  and  physical  exertion;  on  the  other  hand. 
when  it  is  specially  interesting  to  the  patient,  she  can  endure  a  considerable 
amount  of  exertion,  as.  for  instance,  in  dancing,  as  has  been  previously  men- 
tioned. [Insomnia  at  night  and  a  heavy  sleepy  condition  in  the  daytime  are 
often  seen  in  chlorosis,  but  some  patients  sleep  excessively. — Ed.] 

As  regards  sensibility,  we  often  find  anesthesia  of  different  parts  of  the 
skin  as  well  as  of  the  mucous  membranes,  for  example,  of  the  pharynx;  in 
other  cases  there  is  hyperesthesia,  and  especially  neuralgic  phenomena  in  the 
distribution  of  different  nerves.  Intercostal  neuralgia  is  quite  common,  and, 
if  it  occur  on  the  left  side,  is  often  incorrectly  referred  to  the  spleen  as  the 
so-called  "  splenalgia"  of  which  the  patients  complain. 

Motor  disturbances,  also,  are  often  accompanying  symptoms.  Paresis  of 
the  various  muscles  of  the  larynx  and  also  of  those  of  the  extremities  is  often 
found. 

The  condition  of  the  reflexes  varies;  they  are  frequently  normal,  some- 
times diminished,  in  other  cases  exaggerated. 

Moreover,  disturbances  of  the  sympathetic  system  manifesting  themselves 
by  an  abnormal  innervation  of  the  blood-vessels  are  very  important.  Thus 
we  may  observe  in  these  patients  an  abnormal  facility  for  blushing  followed 


THE   BLOOD  325 

by  a  rapidly  succeeding  pallor.  The  appearance  of  erythematous  areas  upon 
the  trunk  may  also  be  grouped  with  these. 

Disturbances  of  the  organs  of  special  sense,  particularly  often  that  of 
vision,  manifesting  itself  by  the  fact  that  the  patient-  soon  tire  in  reading, 
.-«■wing,  etc.,  in  most  cases  are  caused  by  weakness  of  the  eye-muscles  and  of 
the  mechanism  of  accommodation. 

Besides  this,  in  many  instances,  serous  infiltrations  of  the  retina  are  found, 
which  then  appears  strikingly  pale,  and,  especially  about  the  papilla,  lacks 
distinct  contour,  and  look-  a-  if  Loosened. 

Now  and  then  attacks  of  transitory  blindness  or  partial  deficiencies  in 
vi>ion  are  noticeable,  which,  although  they  greatly  alarm  the  patient,  offer  a 
good  prognosis  and  disappear  completely. 

Anomalies  of  taste  have  already  been  mentioned.  We  also  find  abnormal- 
ities of  smell,  the  same  as  in  hysteria. 

THE   BLOOD 

Tin:  BLOOD  OF  CHLOROTIC8  has,  for  a  very  long  time,  been  the  subject  of 
thorough  and  extensive  researches,  and  even  with  the  naked  eye  the  watery 
appearance  and  the  marked  pallor  of  the  blood,  which  flows  freely  from  the 
slightest  puncture,  is  conspicuous.  If  hlood  of  this  kind  is  diluted  with  a 
definite  quantity  of  water,  and  this  mixture  is  compared  with  a  similar  dilu- 
tion of  a  like  quantity  of  normal  hlood.  the  difference  in  color  is  \<-vy  deeided  ; 
this  is  also  shown  by  all  the  various  instruments  which  are  constructed  for 
the  same  purpose,  i.e..  for  comparison,  by  mean.-  of  transmitted  light,  of  the 
color  of  the  blood  with  a  standard  color,  the  so-called  Jiemoglobinometer,  so 
a-  to  determine  a  decided  reduction  of  the  coloring  matter  of  the  hlood. 

The  exact  estimation  of  the  amount  of  hemoglobin  from  the  amount  of 
iron  contained  in  the  hlood  also  -hows  a  considerable  reduction  of  the  iron 
and  hemoglobin  values,  so  thai  there  can  be  no  doubl  thai  in  chlorosis  there 
is  a  considerable  redaction  of  the  hemoglobin  percentage. 

In  opposition  to  this,  it  is  of  special  interest  that  the  count  of  red  hlood 
cells,  which  in  the  course  of  time  ha-  been  made  in  many  cases  and  from 
differenl  standpoints,  -how-  in  the  majority  of  cases  of  uncomplicated  chlorosis 
no  considerable  reluct  inn  in  I  he  number  of  these  cells,  which  are  the  carriers 
of  the  hemoglobin,  and  it  can  he  stated  positively  to-day  thai  ;i  reduction  in 
the  number  of  these  cells,  an  "  oligocythemia"  is  not  present  in  chlbr 
The  normal  Dumber  of  red  corpuscles  in  a  cubic  millimeter  of  woman's  hlood 
i-  about  1,500,000;  in  chlorotic-  we  lind  an  average  of  from  3,800,000  to 
4,000,000,  and  in  some  cases  even  an  almosl  normal  number;  while  a  marked 
reduction  in  the  number  of  red  hlood  cell-  i-  found  only  in  such  chlorotics 
as  are  debilitated  in  consequence  of  a  prolonged  duration  of  the  disease,  insuffi- 
cienl  nutrition  and  complications  of  some  kind. 

These  two  important  fact-,  that,  on  the  one  hand,  the  amount  of  hemo- 
globin is  always  considerably  reduced,  sometimes  to  a  third  of  the  normal, 
while  the  number  of  red  blood  cell-  i-  changed  hut  very  little,  allow  as  t" 
conclude  positively,  that  some  individual  rid  blood  cells  must  he  p,>,,rer  in 


326  CHLOROSIS 

hemoglobin.  Therefore,  we  designate  this  peculiar  form  of  anemia  in  chloro- 
sis as  an  "  oligochromemia"  that  is,  a  deficiency  in  the  hemoglobin  of  the 
blood.  This  symptom  forms  one  of  the  most  important  characteristics  of  the 
blood  of  chlorotics,  and  is  only  seldom  found  so  pronounced  in  the  other 
anemias.  [In  my  experience  "chlorotic  blood" — excessively  low  color-index 
— is  not  at  all  uncommon  in  other  forms  of  anemia,  e.  g.,  in  "  splenic  anemia," 
malarial  anemia,  cancerous  anemia,  post-hemorrhagic  anemia,  etc.  Chlorotic 
blood  is  in  no  way  peculiar. — Ed.] 

If  attention  be  directed  to  the  cells  of  the  blood  themselves,  we  find  the 
view  corroborated,  even  on  examination  of  the  unstained  preparation;  each 
individual  red  cell  has  sustained  a  considerable  loss  in  its  hemoglobin.  The 
majority  of  these  cells  appear  strikingly  pale,  and  absorb  stains  very  imper- 
fectly, a  sign  that  the  quantity  of  coloring  hemoglobin  in  the  cells  has  been 
considerably  reduced. 

Morphologically  we  find  striking  differences  in  the  size  of  the  red  blood 
cells.  Many  of  them  appear  remarkably  large  (macrocytes)  and  at  the  same 
time  quite  pale,  without  a  distinctly  pronounced  central  umbilication — as 
though  swollen.  These  large,  pale  discs  have  been  designated,  quite  appro- 
priately, "  chlorotic,"  blood-corpuscles.  Still  other  cells,  on  the  contrary,  are 
distinguished  by  their  diminutive  size  {micro cyt es) .  [Finnish  observers  have 
proved  that  the  average  diameter  of  the  red  corpuscles  in  chlorosis  is  often 
diminished.  The  cells  grow  smaller  as  the  disease  is  aggravated,  and  return 
gradually  to  their  normal  size  in  convalescence. — Ed.] 

The  stained  cells  show  very  distinctly  the  anomaly  designated  polychro- 
matophilia;  that  is,  they  partially  take  up  the  basic  stains  instead  of  acid 
stains;  and,  therefore,  the  stained  preparation  has  a  peculiar  appearance 
characterized  by  the  fact  that  many  large  cells,  very  faintly  stained  erythro- 
cytes, alternate  with  many  small  intensely  stained  cells,  and  with  cells  showing 
polychromatophilia. 

On  the  other  hand,  genuine  phenomena  of  degeneration,  such  as  po'ikilo- 
cytosis  and  granular  "  degeneration  "  (the  presence  in  the  red  cells  of  numer- 
ous, very  small,  basophilic  granules),  do  not  belong  to  the  blood  picture  of 
chlorosis,  but  occur  only  in  very  far  advanced  cases  of  this  kind  when  decided 
disturbances  of  nutrition  are  present,  or  complications  which  lead  to  cachexia ; 
as,  for  instance,  habitual  constipation  with  increased  intestinal  decomposition. 

In  the  same  manner,  nucleated  red  blood  cells  are  not,  as  a  rule,  present 
in  chlorosis,  but  occur  only  in  the  extreme  grades  of  the  disease  when  intense 
irritation  of  the  hematopoietic  organs,  i.  e.,  of  the  hone-marrow,  has  taken 
place. 

The  condition  of  the  leukocytes  in  chlorosis  is  not  uniform.  It  may  be 
stated  positively  that  these  ceils  do  not  show  any  characteristic  change  in  this 
disease.  Very  often  their  number  is  increased;  especially  during  those  stages 
of  the  disease  in  which  regenerative  processes  in  blood  production  are  mani- 
fested by  other  signs  as  well  as,  for  instance,  by  the  appearance  of  nucleated 
erythrocytes. 

In  the  experience  of  the  author,  no  new  cell  forms  appear  in  this  variety 
of  leukocytosis;  but  we  have  rather  to  deal  with  an  increase  in  number  of 


THE  BLOOD  327 

the  normal  forms  of  leukocytes,  and  by  preference  with  an  increase  in  the 
number  of  polynuclear  neutrophilic  forms  and  of  the  lymphocytes,  while  ab- 
normal forms,  as,  for  instance,  the  myelocytes  (large  leukocytes,  with  one 
nucleus  and  with  neutrophilic  granules)  belong  to  the  exceptions. 

To  sum  up,  we  may  say  that  the  leukocytes  do  not  play  a  role  of  any 
importance  in  the  blood  changes  of  chlorosis. 

The  third  formed  constituents  of  the  blood,  the  so-called  "  blood  plaques," 
attract  especial  attention  in  chlorosis  because  here  they  appear  in  remarkably 
increased  numbers,  so  that  large  groups  of  these  small  colorless  structures 
may  often  be  seen  in  each  field  of  the  fresh  preparation. 

We  are  still  uncertain  as  to  t heir  significance.  Some  authors,  for  instance, 
the  pupils  of  Arnold,  consider  them  as  a  segmentation  product  of  the  red 
blood  colls,  while  others  believe  them  to  be  fragments  of  disintegrated  nuclear 
substance. 

Since  these  small  bodies,  as  I  have  repeatedly  noted  in  many  examinations, 
may  be  partially  stained  with  basic  stains,  especially  well  with  methylene- 
blue,  and  partially  with  certain  nuclear  stains,  for  instance,  with  Ziemann's 
[or  Irishman's]  eosin  methylene-blue  mixture,  I  believe  that,  at  least  in  the 
majority  of  cases,  they  may  be  considered  fragments  of  nuclear  substance,  and 
at  best  only  a  small  number  of  them  may  have  originated  from  red  blood  cells. 

In  any  case,  our  knowledge  concerning  these  small  structures  is  so  indefi- 
nite that  from  their  appearance  in  increased  numbers  in  the  circulating  blood 
we  cannot  draw  any  conclusion,  cither  general  or  special,  in  regard  to  chlorosis. 

In  uncomplicated  cases  of  chlorosis,  the  blood  scrum  shows,  as  a  rule  no 
noteworthy  reduction  in  the  percentage  of  albumin.  The  specific  gravity  of 
the  serum  is  on  the  average  L.028,  which  corresponds  perfectly  with  the  com- 
position of  normal  serum,  and  the  total  solids  appear  to  be  normal  in  amount, 
averaging  about  10  per  cent.  [The  greatest  menace  to  the  life  of  the  chlorotic 
is  thrombosis  of  the  cerebral  sinuses.  Venous  thrombosis  of  the  extremities 
is  also  much  commoner  than  in  any  other  form  of  anemia.  As  a  rule,  throm- 
bosis occurs  in  the  severesl  and  most  chronic  cases.  It  is  very  possibly  con- 
nected with  the  excess  of  platelets  in  the  blood. — Ed.] 

Taking  into  consideration  all  these  changes,  it  follows  that  the  blood  in 
chlorosis  is  of  a  peculiar  composition,  and  characterized  by  the  fad  thai  the 
normal  number  of  blood  cells  is  only  very  slightly  reduced  while  the  amount 
of  hemoglobin  of  the  individual  cell  is  considerably  diminished,  and  thus  a 
peculiar  relationship  between  the  fluid  constituents  of  the  blood  and  I  In'  blood 
cells  develops,  which  is  surprisingly  manifest  if  we  puncture  a  vein  in  the 
arm.  permit  a  feu  cubic  centimeters  of  blood  to  How  into  a  tube,  and  centrifu- 
gate  it  before  it  coagulates.  In  doing  this  we  notice  (as  also  when  we  allow 
the  blood  to  coagulate  spontaneously  or  to  form  a  sediment)  llml  the  mass 
of  Ihr  red  tells,  iu  lolo.  is  extraordinarily  reduced,  often  lo  only  25  per  cent. 
of  Hie  whole  bloml  muss,  compared  with  1">  per  cent,  of  the  blood  /hud.  while 
in  normal  blood  both  components  «ire  present  in  about  equal  proportions. 

It  is  obvious  from  (he  above  mentioned  examinations  that  the  blood  cells, 
although  present  in  aboul  normal  numbers,  are  markedly  deficient  in  hemo- 
globin,  while   the  chief   hulk   of   the  blood    is    formed    hv    pla-mia.   BO   that    this 


328  CHLOROSIS 

condition  of  the  blood  has  been  properly  designated  "polyplasmia"  that  is, 
an  increase  of  the  total  amount  of  plasma  in  contrast  with  other  changes  of 
the  blood,  such  as  are  found,  for  instance,  in  chronic  circulatory  disturbances 
in  consequence  of  heart  or  lung  diseases,  in  which  the  volume  of  the  blood 
cells  exceeds  by  far  that  of  the  plasma,  and  in  which,  therefore,  a  condition 
of  "  oligoplasmia,,  is  present.  [The  researches  of  Haldane  and  Smith  re- 
garding the  total  volume  of  the  blood  in  chlorosis  as  measured  by  capacity 
to  absorb  CO  gas  point  to  the  same  polyplasmia  referred  to  by  Grawitz. — Ed.] 
All  these  changes  must  be  carefully  considered,  as  they  point  the  way  to 
a  more  thorough  understanding  of  the  pathologic  process  in  chlorosis,  as  we 
shall  see  later.  However,  the  circumstances  in  all  cases  are  by  no  means  so 
simple  and  so  distinctly  pronounced  that  we  are  able  to  make  the  diagnosis 
of  chlorosis  from  the  blood  changes  alone.  We  must  emphasize  explicitly 
that  in  general  practice  the  blood  examination  can  only  confirm  the  diagnosis; 
tin1  disease  itself  can  only  be  diagnosticated  by  taking  into  consideration  all  the 
preciously  described  symptoms. 

In  conclusion  let  us  review  the  entire  symptomatology  of  chlorosis,  and 
compare  it  with  that  of  simple  anemia,  for  example — to  choose  the  simplest 
form — post-hemorrhagic  anemia,  such  as  develops  after  repeated  hemorrhages 
from  the  stomach  or  the  uterus. 

In  simple  anemia  we  find  general  pallor,  extension  of  the  cardiac  dulness, 
systolic  murmurs  and  also  venous  murmurs  as  in  chlorotics;  in  addition  the 
signs  of  anemia  of  the  brain  are  found,  specks  before  the  eyes,  vertigo  and 
syncope.  On  the  other  hand,  if  there  are  no  complications,  the  entire  group 
of  nervous  symptoms  are  lacking  in  simple  anemia,  especially  anomalies  in 
the  psychical  sphere  and  of  the  appetite;  in  spite  of  the  increased  frequency 
of  the  pulse,  as  the  result  of  anemia,  the  troublesome  cardiac  palpitations  are 
absent,  as  are  also  the  symptoms  referable  to  the  sensory  sphere  and  the 
vasomotor  tissue  which  give  to  chlorotics  their  peculiar  puffy  appearance. 

The  changes  in  the  blood,  too,  are  essentially  different,  for  in  simple  anemia 
following  hemorrhage  we  always  find  a  considerable  reduction  in  the  number 
of  cells,  while  the  amount  of  hemoglobin  in  the  individual  cell  is  only  slightly 
or  not  at  all  decreased.  [This  is  true  immediately  after  the  bleeding.  Later, 
the  amount  of  hemoglobin  becomes  relatively  diminished,  and  the  blood  may 
simulate  closely  the  conditions  found  in  chlorosis. — Ed.]  On  the  other  hand, 
the  serum  in  these  anemias  always  shows  a  more  or  less  considerable  diminu- 
tion in  the  percentage  of  albumin,  so  that  these  two  main  factors,  the  blood 
cells  and  the  blood  serum,  are  entirely  different  from  those  of  chlorosis. 
Moreover,  in  anemias  following  severe  hemorrhage  we  find  nucleated  red 
corpuscles  and  an  increase  in  the  number  of  leukocytes.  [Post-hemorrhagic 
leukocytosis  is  a  curiously  inconstant  phenomenon.  As  a  rule  it  occurs,  not 
immediately  after  the  hemorrhage,  but  some  days  later,  and  its  duration  is 
very  variable.  Unless  frequent  examinations  are  made  the  wave  of  increase 
is  often  missed  altogether. 

The  same  is  true  of  the  "  shower  "  of  normoblasts  which  usually  occurs 
after  hemorrhage,  but  may  be  very  brief. — Ed.] 


PATHOLOGICAL  ANATOMY  329 


PATHOLOGICAL  ANATOMY 


The  analontiral  lesions  of  this  disease  have  by  no  means  been  determined 
with  certainty.  The  great  difficulty  in  making  positive  statements  regarding 
organic  changes  in  chlorosis  lies  in  the  fact  that  in  uncomplicated  chlorosis 
fatal  cases  are  exceedingly  rare,  and  we  are  consequently  dependent  upon  the 
scant  observations  obtained  when  chlorotics  have  perished  from  an  intercur- 
rent disease,  and  in  these  cases  we  are  compelled  to  decide  which  among  the 
organic  changes  are  to  l>e  referred  to  chlorosis  and  which  are  to  be  attributed 
to  the  affection  causing  the  fatal  issue. 

In  these  cases,  changes  in  the  hematopoietic  apparatus  of  chlorotics,  that 
is,  in  the  marrow  of  the  long,  tubular  funics,  which  might  be  held  responsible 
for  the  origin  of  the  blood  changes,  are  as  yet  not  understood.  The  author 
himself  examined  thoroughly  the  tibiae  of  two  chlorotic  girls,  and  was  unable 
to  find  any  disease  changes,  macroscopically  or  microscopically,  in  the  distri- 
bution of  the  red  and  l'at  marrows. 

Besl  known  are  the  changes  in  Ihr  (initiatory  apparatus,  presented  by 
Virchow  as  the  anatomical  foundation  of  chlorosis,  and  which  for  a  long 
time  were  interpreted  in  this  sense  by  clinicians.  According  to  Virchow.  we 
are  dealing  in  these  cases  with  a  defective  development  of  tin1  heart  and  of 
the  large  arterial  vessels,  with  a  hypoplasia  or  dwarfed  stair  in  which  the 
changes  in  the  vessels  become  manifest  by  abnormal  narrowing,  thinness,  and 
elasticity  of  the  arteries,  and  also  by  irregular  ramifications  of  the  vessels. 

This  hypoplasia  of  the  heart  and  vascular  system,  as  Virchow  teaches. 
favors  the  assumpl  ion  of  a  predisposil  ion.  either  congenital  or  acquired  in  early 
youth,  which,  as  a  rule,  causes  actual  disturbances  having  pathological  im- 
portance only  at  puberty,  and  that  chlorosis  itself,  though  incurable,  may,  I»;/ 
proper  treatment,  particularly  Inj  dietetic  measures,  he  kept  in  a  state  of 
latency. 

These  hypoplasias  of  the  heart  and  valvular  system  subsequently  became 
matters  of  greal  importance,  und  the  narrow,  thin-walled  and  enormously 
elastic  aorta  has  briefly  been  designated  "aorta  chlorotica"  without  at  all 
explaining  how  a  diminished  amount  of  hemoglobin  in  the  blood  can  result 
from  narrowness  of  the  vascular  system,  secondly,  why  the  chlorotic  symp- 
tom-complex can  in  many  cases  he  so  readily  and  permanently  overcome,  and. 
finally,  the  important  question  why  men  win»,  according  to  Virchow,  also 
frequently  suffer  from  hypoplasia  of  the  heart  and  of  the  arteries,  are  so 
rarely  attacked  inj  chlorosis.  In  regard  to  this  latter  point  particularly,  i.e.. 
the  rare  occurrence  of  chlorosis  in  men.  it  i-  remarkable  that  Virchow  disre- 
garded this  in  his  hypothesis,  in  spite  of  frequent  anatomically  recognizable 
changes  in  the  vascular  system. 

A-  a  matter  of  fact,  in  many  chlorotics,  hypoplasia  of  the  heart  and  of 
the  vessels  certainly  plays  an  important  role,  hut  only  in  so  far  a-  it  represents 
an  irreparable  and,  therefore,  very  unfavorable  complication  of  chlorosis;  for 
in  this  condition  we  are  dealing  with  a  faulty  structure  <>f  the  vascular  system 
which   is  acquired    in   early  youth,   wrhich   cannot   of   it-elf   lead   to  chlorotic 


330  CHLOROSIS 

blood  changes,  i.  e.,  decrease  in  the  amount  of  hemoglobin,  but  which  in  all 
likelihood  brings  with  it  another  pathological  condition  of  the  blood  which 
we  must  designate  as  oligemia  vera,  i.  e.,  a  decrease  in  the  total  mass  of 
the  blood. 

Such  persons  with  lessened  capacity  of  the  heart  and  of  the  vessels  and 
probably  of  a  lessened  total  quantity  of  blood,  may,  provided  they  do  not 
over-exert  themselves,  appear  to  be  quite  healthy;  and,  as  a  matter  of  fact, 
we  are  very  frequently  surprised  to  find  this  state  of  affairs  in  a  well  developed 
form  at  the  autopsy  of  persons  in  whom  we  could  not  suspect  an  anomaly  of 
the  vascular  system. 

In  itself  it  is  quite  unlikely  that  hypoplasia  of  the  vascular  system  is  capa- 
ble of  producing  chlorosis.  It  can  at  most  be  looked  upon  as  a  predisposing 
factor;  aside  from  this  it  certainly  plays  an  important  role  in  those  chlorotics 
who  show  an  abnormal  tendency  to  relapses,  characterized  by  very  slight 
inclination  to  improvement,  so  that  such  cases  have  also  been  designated  as 
''habitual"  and  "  persistent"  chlorosis. 

At  the  present  time  it  may  be  maintained  with  certainty,  that  the  severe 
anatomical  changes  of  the  vascular  system  are  not  characteristic,  nor  are  they 
even  the  specific  anatomical  foundation  of  chlorosis.  In  our  further  discus- 
sion, we  shall  have  to  consider  their  effect  as  factors  in  prognosis  and  treat- 
ment. 

Similar  hypoplastic  changes  have  also  been  found  in  the  genital  organs, 
and  these  changes  have  also  been  considered  to  bear  a  causal  relation  to 
chlorosis.  Yet  here  we  may  hold  the  same  view  as  in  the  hypoplasia  of  the 
vascular  system,  that  these  anomalies  are  to  be  looked  upon  only  as  predis- 
posing factors,  and  that  they  cannot  be  regarded  as  an  explanation  of  the 
entire  symptom-complex,  especially  of  the  blood  changes. 

All  other  changes,  such  as  degeneration  of  the  heart  muscle,  parenchyma- 
tous inflammation  of  the  kidneys,  and  other  anatomical  alterations,  are  to  be 
considered  as  secondary.  Hence  it  must  be  admitted  that  at  the  present  time 
a  definite  anatomical  cause  of  this  disease  is  absolutely  unknown. 

FREQUENCY   OF   CHLOROSIS   WITH   REGARD   TO 
SEX,    AGE    AND    LOCALITY 

It  has  been  noticed  for  many  years  that  chlorosis  affects  preferably  the 
female  sex.  There  are,  however,  undoubtedly  cases  of  genuine  chlorosis  in 
young  men,  all  the  symptoms  of  the  disease  most  distinctly  presenting  them- 
selves, in  the  1  flood  as  well  as  in  the  other  organs.  As  Wunderlich  has 
observed,  the  symptom-complex  is  noted  usually  in  young  men  of  poor 
physique  and  of  sedentary  occupation — tailor-apprentices,  office  clerks,  etc. 
[See  Editorial  Note  II  on  p.  320. — Ed.]  We  do  not  as  yet  know  whether  or 
not  the  above  mentioned  changes  in  the  heart  and  vascular  system  are  already 
existent  in  those  cases  and  predispose  to  the  outbreak  of  the  disease. 

The  age  at  which  chlorosis  appears  in  the  great  majority  of  cases  is  that 
of  puberty,  from  the  twelfth  or  fourteenth  year  to  the  twentieth.  [From 
eighteen  to  twenty-three  is,  in  my  experience,  the  period  in  which  the  great 


PREDISPOSING  INFLUENCES  331 

majority  of  cases  occur.  Immediately  after  the  establishment  of  menstruation 
chlorosis  is  rare.  An  interval  of  five,  or  even  ten,  years  often  follows. — Ed.] 
The  disease  does  appear,  however,  in  young  children,  or,  on  the  other  hand, 
and  this  is  not  infrequent,  may  occur  in  the  twenties;  after  the  thirtieth  year 
chlorosis  is  exceedingly  rare,  either  as  a  primary  or  recurrent  attack. 

Concerning  the  constitution  it  may  be  -aid  that  young,  delicately  traut 
girls,  weak  in  muscle,  but  comparatively  fat.  are  most  likely  to  be  affected 
with  chlorosis;  on  the  other  hand,  the  robust  constitution  of  a  girl  raised  in 
the  country,  for  instance,  a  servant,  offers  no  protection  against  the  appear- 
ance of  this  disease.  It  must  be  confessed,  however,  that  when  chlorosis 
appears  in  girls  of  the  latter  type,  as  a  rule  it  is  milder,  and  can  be  remedied 
sooner  and  more  surely  than  in  those  with  a  delicate  constitution. 

Whether  chlorosis  occurs  more  often  in  certain  localities  than  in  others 
is  difficult  to  determine,  for  it  is  almost  impossible  to  obtain  positive  statistics 
of  this  disease,  and  especially  because  many  physicians  include  under  the 
name  of  chlorosis  all  varieties  of  anemia  in  young  girls.  It  is  certain  at  any 
rate  that  the  disease  is  more  frequent  in  large  cities  than  in  the  country. 

PREDISPOSING   INFLUENCES 

Many  factors  may  be  looked  upon  as  predisposing  causes  of  chlorosis,  and 
a  knowledge  of  these  is  of  the  utmost  importance  for  the  thorough  compre- 
hension of  the  entire  picture  of  the  disease  on  the  one  hand,  as  well  as  for 
the  treatment  on  the  other  hand. 

These  deleterious  predisposing  influences  are  to  be  found,  first,  in  the 
domain  of  general  hygiene,  and,  secondly,  among  certain  organic  diseases. 

In  the  first  group,  i.e..  the  hygienic  influences,  we  m   include  errors 

in  physical  and  mental  training,  which,  especially  among  the  higher  clas 
are  of  great  social  importance. 

Here,  to  cite  a  very  frequent  error,  we  observe  a  neglect  of  the  physical 
development  of  growing  girls  as  compared  with  that  of  hoys.  Out  of  regard 
for  their  <\v~~.  they  are  not  permitted  to  romp  freely,  but  are  taken  oul  to 
walk  by  the  side  of  a  governess;  they  are  qoI  sufficiently  in  the  fresh  air.  and 
have  no  opportunity  of  enjoying  a  rapid,  powerful  and  invigorating  exercise 
of  the  muscles. 

When  we  consider  the  view  of  Virchow,  previously  referred  to,  that  hypo- 
plasia of  the  heart  and  of  the  \a-cular  system  is  partially  acquired  in  intra- 
uterine life  but  i-  specially  developed  in  extra-uterine  existence,  the  tb.OUgb.1 
involuntarily  arises  that,  in  many  cases,  this  lach  of  development  of  the  heart 
and  vessels  may  be  due  to  the  fact  that  the  normal  stimulus  for  such  n  develop- 
ment of  the  vascular  system  as  is  unquestionably  necessary  for  free  movi  ment 
of  the  muscle  masses  in  the  limbs  and  trunk  is  in  these  children  not  sufficiently 
active,  and  that  this  faulty  development  of  the  circulator]  apparatus  may, 
perhaps,  be  considered  a  form  of  inactivity  hypoplasia.  |lf  this  be  true,  the 
apparenl  diminution  in  the  number  of  cases  of  chlorosis  presenting  themselves 

at   our  clinic-  might   be  explained   by  the  more  active  habits  of  life  which   ar< 

certainly  prevalent  in  America  in  the  present  decade. — Ed.] 


332  CHLOROSIS 

As  already  remarked,  although  the  whole  complex  of  symptoms  in  chlorosis 
cannot  be  explained  by  these  anatomical  changes,  yet  they  surely  form  pre- 
disposing factors,  and  moreover,  as  we  shall  observe  later,  chlorosis  is  undoubt- 
edly more  severe  in  these  abnormally  organized  girls  than  in  those  with  a 
normal  circulatory  system. 

Still  more  injurious  is  the  pernicious  habit  of  allowing  young  girls  to  wear 
tightly  laced  corsets  which  compress  the  lower  parts  of  the  thorax,  hinder 
respiration  and  the  circulation  of  the  blood,  and  unquestionably,  besides  pro- 
ducing the  well-known  changes  in  the  liver,  lead  to  alteration  of  position, 
and  prevent  the  motility,  of  the  stomach.  [That  tight  lacing  has  any  definite 
relation  to  chlorosis  is,  I  think,  quite  unproved,  though  many  writers  refer 
to  it. — Ed.] 

Other  injurious  causes  are  to  be  found  in  the  nutrition;  these  consist  of 
disturbances  of  digestion  with  a  loss  of  appetite  for  wholesome  food;  instead 
of  nourishing  the  young  girl  with  milk  and  other  easily  digested  and  nutri- 
tious food,  she  is  allowed  to  feed  upon  dainties. 

Among  the  lower  classes,  unhygienic  conditions  of  living  are  frequently 
at  fault;  growing  up  in  damp,  badly  ventilated  rooms  into  which  the  rays 
of  the  sun  rarely  penetrate,  eating  insufficiently  and  of  indigestible  food,  are 
conditions  potent  as  predisposing  causes  of  chlorosis.  [It  has  still  to  be 
shown,  I  think,  that  bad  hygiene  can  or  does  produce  any  type  of  anemia. 
It  is  natural  to  expect  that  anemia  would  result  from  such  conditions,  but  I 
have  never  seen  any  good  reason  to  believe  that  it  does. — Ed.] 

In  all  classes,  premature  indulgence  in  alcohol  must  be  considered;  this  is 
often  permitted  children  through  mistaken  dietetic  principles,  but  conduces 
to  the  undermining  of  the  health  at  an  early  age. 

To  these  faults  in  training  psychical  factors  are  added,  such  as  the  prema- 
ture awakening  of  sensuality  by  exciting  literature,  exaggerated  novels  and 
the  like,  from  which  ideas  of  love  develop  entirely  too  early  and,  in  many 
cases,  not  only  exert  an  unwholesome  influence  upon  the  psychical  nature, 
but  upon  the  whole  physical  condition. 

A  peculiar  predisposition  favoring  the  development  of  chlorosis  may  be 
observed  daily  in  the  life  of  a  large  city.  This  is  manifested  in  young  servant 
girls,  who,  as  a  rule  to-day,  come  from  the  country  or  from  small  towns  to 
the  large  cities  in  quest  of  higher  wages,  and  often,  after  a  brief  residence, 
suffer  from  well-developed  chlorosis.  This  contingent  of  young  girls  forms 
a  large  proportion  of  our  hospital  patients,  and  it  is  interesting  to  inquire 
into  their  history.  Usually  we  find  that  these  girls,  on  the  average  from 
eighteen  to  twenty-two  years  of  age.  were  while  at  home  always  well,  strong, 
and  able  to  work,  as  may  also  be  inferred  from  their  "  service  books."  After 
arrival  in  the  large  city,  a  very  brief  period  sometimes  elapses  before  they 
become  ill  and  show  the  fully  developed  symptom-complex  of  chlorosis. 

The  author  has  taken  special  interest  in  these  cases,  and  after  careful 
investigation  has  found  that  two  to  four  weeks  are  often  sufficient  to  transform 
a  healthy  and  robust-looking  girl  into  a  patient  with  pronounced  symptoms 
of  chlorosis.  It  is  worthy  of  note  that  these  patients  manifest  no  anomalies 
of  the  stomach  or  intestines  except,  perhaps,  transitory  constipation,  nor  any 


THE  GENESIS  OF  CHLOROSIS  333 

disturbances  of  the  sexual  functions,  a  point  which  is  important  for  the  com- 
prehension of  the  entire  process. 

As  factors  which  favor  the  outhreak  of  the  affection  we  may  mention 
the  changes  in  the  food  and  in  the  mode  of  life,  particularly  the  late  going 
to  bed  and  the  hard  work  (the  climbing  of  many  flights  of  stairs).  Other 
causes  which  play  an  important  role  are  the  hurry  of  life,  psychical  exaltation, 
especially  nostalgia,  and  finally  reduced  consumption  of  fresh  air. 

(Vrtainly.  it  is  undeniable  thai  the  mere  removal  of  a  previously  perfectly 
healthy  young  girl  from  the  country  to  a  large  city  is  sufficient  to  produce  the 
entire  symptom-complex  of  chlorosis,  and  that  the  same  girl,  if  senl  back  to 
her  former  country  home,  will  lose  every  trace  of  the  disease;  for  this  reason 
the  author  suggests  the  name  "  city  chlorosis  "  for  this  variety  of  the  affection. 

Besides  these  factors,  organic  diseases  may  lead  to  the  development  of 
chlorosis.  As  an  instance,  we  may  mention  " gastroptosis "  with  the  digestive 
disturbances  that  accompany  it.  Meinert,  especially,  has  called  the  attention 
of  the  profession  to  its  frequent  presence  in  chlorosis. 

Menstrual  abnormalities,  too,  particularly  profuse  menstruation,  certainly 
predispose  to  chlorosis,  as  also  prohahly  does  an  attack  of  an  acute  infectious 
disease. 

Reviewing  at  a  glance  all  these  predisposing  factors,  beginning  with  the 
anatomical  changes  of  the  circulatory  apparatus,  then  the  unhygienic  influ- 
ences, and,  finally,  actual  organic  diseases,  it  is  at  once  apparent  that  there 
exists  no  specific  factor  nor  one  single  factor  which  is  found  as  the  cause  in 
all  cases,  but,  on  the  contrary,  taking  into  consideration  the  great  variety  of 
predisposing  causes,  we  have  reason  to  believe  that  the  point-  of  minor  resist- 
ance that  favor  the  outhreak  of  this  peculiar  disease  are  manifold.  The 
question  arises  which,  in  this  large  number  of  diversified  and  detrimental 
influences,  is  I  he  connecting  link  that  may  satisfactorily  explain  th- 
and  the  true  nature  of  Ihr  disease. 

THE    GENESIS   OF   CHLOROSIS 

The  views  that  have  been  expressed  with  regard  to  the  development  and 
the  true  aature  of  this  disease  vary  greatly.  First,  the  theory  is  to  he  consid- 
ered which   treats  of  chlorosis  as  an   essential  blond  disease,   in   which   all 

■  nie  changes  or  Bymptoms  on  the  part  of  the  organs  are  of  a  secondary 
nature,  ami  the  blood  itself  is  the  primary  senl  of  the  disease.  This  view 
is  no  longer  tenable  on  account  of  the  numerous  and  exact  blood  examina- 
tions that  have  been  made  in  the  last  \'rw  decades,  the  results  of  which  have 
been  mentioned  above.  According  to  oar  present  knowledge,  u  specific  dis- 
ease of  Ihe  hlood  niiisl  of  necessity  be  combined  with  changes  of  the  blood 

cells,  and.  us  ire  hure  noted,  Ihere   is  absolutely  no  support  for  this   mir.  8tnC( 

tin  principal  "ml  most  important  morphological  changes  consist  m  n  de,  ■ 
of  the  hemoglobin  of  ihr  blood-corpuscles,  while  degenerative  changes,  a-  well 
;i-  characteristic  pathological  changes  of  the  leukocytes,  are  entirely  absent. 

The  "by,  a,  e  ,,f  pathological  changes  of  the  bone-marrow,  as  we  have  al- 
ready stated,  is  against  the  new  of  a  substantive  blood  disease,  and  another 


334  CHLOROSIS 

point  must  be  particularly  emphasized  to  which  Becquerel  and  Eodier,  the 
celebrated  investigators  in  the  realm  of  hematology,  called  attention  about  the 
middle  of  the  Last  century,  namely,  that  the  changes  in  the  blood  of  chlorotic* 
do  not  correspond  with  the  severity  of  the  clinical  picture;  on  the  contrary. 
particularly  at  the  onset  of  the  disease,  when  all  of  the  other  symptoms  are 
conspicuously  developed,  the  blood  changes  are  comparatively  slight,  and  only 
increase  upon  prolongation  of  the  malady.  This  late  deterioration  of  the 
blood,  according  to  our  present  knowledge,  must  be  referred  partly  to  an 
insufficient  ingestion  of  food,  in  some  cases  also  to  accompanying  symptoms; 
for  example,  to  profuse  menses,  sometimes  perhaps  to  autointoxication  from 
the  intestines.  Therefore,  the  assumption  that  in  chlorosis  the  blood  itself 
is  the  tissue  primarily  diseased  cannot  be  maintained. 

The  development  of  chlorosis  has  been  also  attributed  to  disturbances  in 
the  sexual  functions;  for,  as  previously  remarked,  too  slight  or  too  profuse 
menses  are  observed  in  most  cases  of  chlorosis,  and  Trousseau  actually  refers 
to  Menorrhagie  chlorosis. 

Anatomical  anomalies  of  the  sexual  organs,  which  not  infrequently  appear 
as  hypoplasia  of  these  organs,  have,  as  we  found  to  be  the  case  in  the  circula- 
tory apparatus,  been  looked  upon  as  responsible  for  the  development  of  the 
disease.  Nevertheless,  these  changes  cannot  all  lie  looked  upon  as  special 
causes  of  chlorosis,  but,  at  most,  in  many  cases  as  predisposing  causes.  In 
the  majority  of  instances,  however,  they  are  certainly  secondary  conditions 
in  the  chlorotic  pathological  picture. 

That  these  anomalies  have  no  general  importance  in  the  genesis  of  chlorosis 
may  be  seen  clearly  from  the  fact  that  in  numerous  chlorotics  neither  abnor- 
malities nor  functional  anomalies  of  the  sexual  organs  cm.  at  any  period  of 
the  disease,  be  discovered. 

In  accordance  with  modern  pathological  views,  an  attempt  has  lately  been 
made  to  attribute  to  the  sexual  organs  the  development  of  chlorosis  in  another 
sense.  It  has  been  assumed  that  from  these  organs  (as  we  know  positively  in 
the  case  of  the  thyreoid  gland)  besides  their  well-known  specific  function, 
still  another  internal  secretory  activity  proceeds,  by  means  of  which  materials 
reach  the  circulation,  and  that  this  activity  bears  a  certain  relation  to  the 
hematopoietic  function. 

This  view  is  based  mainly  upon  the  fact  that  chlorosis  is  prone  to  appear 
in  that  period  of  life  in  which  the  sexual  organs  mature.  Yet  it  is  indicative 
of  the  uncertainty  of  these  views  that,  while  v.  Noorden  assumes  that  there  is 
an  absence  of  the  internal  secretion  in  chlorotics,  and  that  as  the  result  of 
this  the  material  reaching  the  blood  is  insufficient  to  stimulate  blood  forma- 
tion, in  opposition  to  this  Lloyd  Jones  holds  the  opinion  that  at  the  time  of 
sexual  maturity  internal  secretions  enter  the  blood  in  superfluous  amounts, 
and  in  some  complicated  manner  bring  about  its  chlorotic  composition. 

These  modern  views  according  to  which  chlorosis  is  attributed  to  the  hypo- 
thetical functional  disturbances  of  the  generative  organs  appear  to  me  as 
untenable  as  the  earlier  ones  which  were  based  upon  anatomic  and  well-known 
functional  disturbances.  I  believe  these  views  of  chlorosis  to  be  just  as  partial 
as  those  concerning  hysteria,  in  which  the  name  at  once  shows  that  the  origin 


THE  GENESIS  OF  CHLOROSIS  335 

of  this  disease  was  formerly  supposed  to  be  in  the  uterine  sphere,  although 
there  can  be  no  doubt  that  in  this  morbid  state  many  hysterical  women  have 
perfectly  normal  sexual  organs  and  functions,  so  that  to-day  no  physician 
seriously  refers  the  symptom-complex  of  hysteria  to  the  uterus. 

Another  opinion  which  was  firmly  maintained  by  Clark  and  Nothnagel  is 
that  in  chlorotic-,  who  almost  invariably  suffer  from  constipation,  there  is  an 
nl, normal  process  of  decomposition  in  the  intestines,  and  from  the  resorption 
of  products  of  this  the  disease  originates. 

This  theory  of  autointoxication,  however,  cannot  be  considered  to  explain 
the  entire  pathological  picture;  indeed  it  may  be  confidently  a— mied  that 
many  chlorotics  never  suffer  from  constipation — neither  before  nor  after  the 
onsei  of  the  disease.  Nevertheless,  I  am  under  the  impression  that  in  some 
cases  of  chlorosis,  autointoxication  from  the  intestines  may  have  an  auxiliary 
deleterious  effect,  and  I  believe  that  various  degenerative  signs  in  the  erythro- 
cytes which  do  not  conform  to  the  ordinary  blood-picture  of  chlorosis  may 
often  be  attributed  to  these  auxiliary  causes. 

Another  theory  as  to  the  etiology  of  chlorosis  has  been  proposed  by  Meinert, 
who.  as  has  been  stated,  lays  special  stress  upon  displacement  and  atony  of  the 
stomach;  this,  in  his  opinion,  develops  a  dragging  of  the  abdominal  sympa- 
thetic, and  is  said  to  cause  anemia,  that  is,  chlorosis. 

In  reviewing  these  theories,  of  which  I  have  indicated  only  the  most  impor- 
tant, it  may  be  noted  that  they  are  alike  unsatisfactory  from  the  circumstance 
that  they  do  not  conform  to  a  uniform  principle,  active  and  pathologic  in  all 
cases,  but,  on  the  contrary,  of  all  of  them  it  ma;/  be  said  that  the  anatomical 
or  functional  changes  considered  to  be  causative  are  in  many  cases  certainly 
not  present. 

When  we  consider  the  characteristic  symptoms  which  distinguish  chlorosis 
from  other  simple  conditions,  and  reflect  that  such  symptoms  can  be  produced 
by  the  nervous  system  exclusively,  and  remember,  on  the  other  hand,  the  pecul- 
iar blood  tinding  which  shows  a  conspicuous  accumulation  of  plasma  in  the 
blood  and  a  decrease  of  hemoglobin  in  the  cells  without  a  diminution  in  the 
number  of  the  cells,  the  conviction  force-  itself  upon  us  that  the  characteristic 
changes  found  in  this  form  of  anemia  must  be  referred  to  the  nervous  system. 
In  my  opinion  chlorosis  depends  more  upon  anomalies  in  the  lymph- 
formation  than  in  tlir  blood-formation;  abnormal  amount-  of  fluid  accumulate 
in  the  tissues  as  well  as  in  the  chlorotic  blood,  as  was  shown  in  the  description 

of  the  symptomatology,  and  in  chlorosis  it  appear-  as  though  the  bl l-vessels 

were  disturbed  in  their  function,  and  the  systematic  exchange  of  fluid  between 
blood  and  tissue  altered;  thus  accumulation-  of  fluid  arise  which,  because  of 
disturbed  Becretory  activity,  are  not  excreted  in  sufficient  amount,  and  in  conse- 
quence lead  to  -t;i-i-  of  the  lymph. 

These  disturbances  in  the  circulation  of  the  blood  and  lymph  are.  in  my 
opinion,  to  be  referred  to  anomalies  in  function  of  the  vasomotor  nerves,  to 

which  also  we  may  refer  the  pallor  and  blushing  that    in  chlorotic-  appear  and 

disappear  bo  rapidly.  Abnormalities  in  the  exchange  of  fluid  between  the 
blood  and  the  tissues  of  the  body  are  especially  dependent  upon  pathological 
functioning  of  the  vasomotor  nervous  system,  as  my  former  investigations 


336  CHLOROSIS 

have  taught  me.  I  believe,  therefore,  that  in  this  direction,  i.  e.,  in  some 
neurosis  of  the  vasomotors,  we  must  search  for  the  explanation  of  the  peculiar 
blood  findings  of  chlorosis,  for  hereby  the  polyplasmia  of  the  blood  and  of 
the  tissues  may  readily  be  explained,  and  it  is  also  perfectly  comprehensible 
that  from  a  general  accumulation  of  fluid  in  the  tissues,  particularly  in  the 
bone-marrow,  the  supply  of  hemoglobin  to  the  erythrocytes  should  be  deficient. 

Chlorosis,  therefore,  I  consider  to  be  a  neurosis,  which  appears  in  young 
adolescents,  not  exclusively,  bat  usually,  in  girls  and  women;  its  development 
being  favored  by  various  preceding,  predisposing  causes.  The  anemic  compo- 
sition of  the  blood  is  simply  one  symptom  of  this  neurosis,  even  though  it  is 
the  most  invariable  and  most  prominent  symptom.  The  origin  of  the  anemia 
may  be  also  referred  to  a  faulty  function  of  the  nerves,  as  also  are  all  other 
nervous  symptoms  which  characterize  chlorosis. 

The  symptomatology,  as  well  as  the  views  regarding  the  etiologic  factors, 
and  also  the  therapeutic  results  which  are  to  lie  later  described,  in  my  judg- 
ment exclude  a  specific  organic  disease  of  the  blood,  as  well  as  the  idea  of  an 
anemia  dependent  on  the  formerly  mentioned  functional  and  anatomical 
anomalies ;  on  the  contrary,  I  believe  chlorosis  to  be  a  link  in  a  chain  of  neu- 
roses particularly  prevalent  in  females,  and  to  represent  a  peculiar  form  of  the 
general  hysteric  symptom-complex. 

DIAGNOSIS 

In  regard  to  the  diagnosis  of  chlorosis,  it  must  first  be  emphasized  that 
the  blood  finding  alone  is  not  decisive  in  the  recognition  of  chlorosis,  as  the 
blood  condition  above  described  occurs  not  only  in  chlorosis,  but  is  occasion- 
ally found  in  other  anemias,  and  therefore  cannot  be  looked  upon  as  typical 
or  pathognomonic.  In  this  disease,  as  well  as  in  other  anemias,  the  blood 
finding  may  be  utilized  to  confirm  the  diagnosis  after  a  previous  general  ex- 
amination of  the  organs,  but,  on  the  other  hand,  the  diagnosis  cannot  be  made 
from  the  blood  condition  and  the  organic  changes  be,  then  made  to  conform  to 
this  finding. 

The  diagnosis  in  well-developed  cases  may  be  readily  made  when  the  dis- 
ease occurs  in  young,  puffy-looking  girls,  with  a  yellowish-green  color  of  the 
skin,  who  present  the  manifold  symptoms  and  anomalies  on  the  part  of  vari- 
ous organs  which  have  been  described.  There  are,  however,  some  difficulties 
here  which  not  infrequently  lead  to  error,  and  are  therefore  of  importance  in 
practice. 

It  must  be  emphatically  pointed  out  that  it  is  a  mistake  to  make  a  diagnosis 
of  chlorosis,  without  further  consideration,  when  young  girls  showing  general 
pallor  come  under  treatment;  on  the  contrary,  this  peculiar  disease  must  be 
distinguished  from  the  usual  forms  of  anemia,  and  here  we  may  consider  par- 
ticularly the  anemia  which  is  the  result  of  internal  hemorrhages,  for  example, 
from  the  menses,  or  hemorrhage  due  to  gastric  ulcer  which,  under  some  cir- 
cumstances, may  produce  even  more  serious  changes  in  the  composition  of  the 
blood  than  chlorosis,  but  which,  for  obvious  reasons,  and  chiefly  from  a  thera- 
peutic standpoint,  must  be  differentiated  from  chlorosis. 


COURSE  OF  THE  DISEASE  337 

The  local  examination  of  the  genital  organs  in  the  one  ease,  or  of  the 
stomach,  the  vomit,  the  feces,  etc.,  in  the  other,  will  guard  us  from  error. 
But  even  before  these  points  are  decided,  chlorosis  may  usually  be  distin- 
guished from  simple  anemias  by  the  great  number  of  pre-eminently  nervous 
and  circulatory  disturbances  which  distinctly  separate  the  one  clinical  picture 
from  the  other. 

There  are  other  organic  diseases  which  often  occur  insidiously  in  young 
girls  and  lead  to  anemia,  so  that  difficulty  in  diagnosis  may  arise,  especially  in 
family  practice  where  the  aid-  to  diagnosis  are  not  so  easily  obtained  as  in  the 
hospital,  and  where  errors  may  more  readily  be  made. 

In  the  first  place  I  shall  name  pulmonary  tuberculosis,  which,  at  the  onset, 
often  causes  but  slight  local  disturbances,  perhaps  only  a  trifling  cough  of 
which  but  little  notice  is  taken.  Xevertheless,  the  affection  in  these  early 
stages  gives  rise  to  a  distinct  anemia.  [It  is  important,  however,  also 
to  recognize  that  intense  pallor  without  any  demonstrable  anemia  is  very 
prone  to  occur  in  tuberculosis. — En.  |  And  it  becomes  an  imperative  duty 
most  carefully  to  examine  the  lungs,  especially  at  the  apices,  in  any  doubt- 
ful case. 

Another  organic  affection,  which  in  practice  frequently  resembles  chloro- 
-i-.  is  chronic  nephritis;  this  is  prone  to  appear  at  puberty  in  those  who,  as 
children,  have  passed  through  an  infectious  disease  and  recovered,  especially 
scarlatina  which  was  later  followed  by  a  sequel — renal  inflammation — the  lat- 
ter, however,  not  having  been  entirely  cured  but,  on  the  contrary,  continuing 
to  affect  the  patient  in  later  life,  although  not  infrequently  the  distinct  sign-. 
particularly  edema,  appear  first  during  puberty.  It  is  therefore  absolutely 
necessary  in  doubtful  cases  to  make  a  careful  examination  of  the  urine," both 
chemically  and  microscopically. 

COURSE    OF    THE    DISEASE 

The  course  of  the  disease  in  individual  cases  shows  great  variation,  and 
from  the  earliest  period-  cases  of  chlorosis  have  been  observed  in  which  there 
was  prompl  improvement,  whereas  others  manifested  a  tendency  to  relapses, 
and  oilier-  again  were  BO  stubborn  as  to  appear  incurable  in  spite  of  any  form 
of  therapy. 

Therefore,  various  forms  of  chlorosis  have  been  differentiated,  such  as 
"transitory"  "relapsing"  <nul  "habitual."  These  variation-  in  the  form  of 
the  disease  can  rarely  be  recognized  at  the  onset.  The  course  is  also  dependent 
on  ;i  variety  of  factor-  30  tbat  these  forms  can  only  be  differentiated  from  one 
another  after  prolonged  observation.  The  mosi  common  form  i-  unquestion- 
ably the  benign  and  transitory,  in  which  all  of  the  symptoms  and  the  blood 
condition  are  relieved  in   the  course  of  a   (c\v  week-. 

The  main  contingent  of  this  group  is  of  course  made  up  of  girls  and  women 
of  ätrong  constitution,  who.  before  the  development  of  chlorosis,  were  com- 
paratively well  ,-md  active.  The  favorable  progress  of  the  disease,  a-  will  be 
more  minutely  demonstrated  in  the  therapy,  is  due  partly  t<>  the  fact  tbat  the 

patient    ig  removed    from   her  11-ual   surroundings,  and    1-  treated    under  COndi- 
28 


338  CHLOROSIS 

tions  which  have  a  beneficial  influence  upon  metabolism  in  general  and  upon 
the  nervous  system. 

The  cases  which  run  an  unfavorable  course,  particularly  those  forms  of 
the  malady  which  are  looked  upon  as  habitual,  i.  e.,  those  not  completely  dis- 
appearing, are  unquestionably  often  complicated  by  anatomical  abnormalities 
such  as  have  been  described ;  for  instance,  by  an  abnormal  smallness  and  nar- 
rowness of  the  heart  and  vascular  system,  and,  probably,  by  an  unfavorable 
predisposition  of  the  hematopoietic  apparatus,  and  a  diminution  in  the  amount 
of  blood.  In  these  cases  we  are  not  dealing  with  pure  chlorosis,  but  with  a 
complicated  anemia  due  to  anatomical  and  chlorotic  changes,  and  in  many 
of  these  instances  Virchow's  opinion  must  be  regarded  as  correct;  namely, 
that  the  chlorotic  symptoms  may  be  suppressed  by  suitable  therapy,  but  the 
disease  can  never  be  entirely  cured. 

It  is  important  to  note  that  these  very  persons  whose  vascular  system  is 
imperfectly  developed  offer  very  slight  resistance  to  other  morbific  and  dam- 
aging influences,  i.  e.,  that  they  are  usually  predisposed  to  catarrhal  affections 
of  the  various  organs,  and  that  they  are  more  subject  to  severe  acute  infectious 
diseases,  as,  for  example,  pneumonia,  etc.,  than  persons  with  a  normally  devel- 
oped vascular  system.  This  fact  explains  the  previously  mentioned  anatomical 
anomalies  found  at  the  autopsy  of  anemic  young  girls. 

Quite  as  obstinate  as  these  mixed  forms  of  oligemia  and  chlorosis  due  to 
anatomical  changes  are  the  forms  of  the  affection  in  early  youth  due  to  such 
errors  in  bringing  up  as  have  been  described — insufficient  nutrition,  deficient 
stimulation  of  the  circulation,  and  undue  irritation  of  the  nervous  system — 
so  that  these  children  from  their  earliest  years  have  never,  in  fact,  had  a  hale, 
hearty,  rosy-cheeked  appearance,  and  have  never  shown  the  normal  mental  and 
physical  vigor  and  sprightliness  characteristic  of  a  well-developed  child  that 
has  received  proper  bringing  up  under  good  management. 

We  meet  such  girls  chiefly  in  private  practice  among  the  better  classes; 
almost  from  infancy  they  are  markedly  languid,  at  school  they  are  less  capable 
of  application,  and  are  easily  fatigued ;  on  the  other  hand,  as  they  grow,  they 
develop  a  special  liking  for  belles-lettres  or  for  books  which  excite  the  imagi- 
nation, and  show  but  slight  inclination  to  exert  their  physical  powers.  It  is 
therefore  quite  possible  that  in  these  girls,  on  account  of  insufficient  muscular 
exercise  and  stimulation,  an  undeveloped  condition  of  the  heart  and  vascular 
system  is  induced,  so  that  in  some  of  them  pure  chlorotic  symptoms  no  longer 
appear,  but  mixed  forms  of  general  anemia  (oligemia)  and  chlorosis. 

It  is  interesting  to  observe  these  girls  when  they  reach  puberty,  marry,  and 
attain  a  riper  maturity.  We  usually  find  that  the  chlorotic  symptoms,  i.  e., 
the  puffy  appearance  and  the  numerous  irregularities  on  the  part  of  the  vari- 
ous organs,  especially  of  the  vascular  system,  disappear.  Nevertheless,  llirsr 
women  remain  pale,  are  inactive,  easily  irritated,  and  form  a  large  proportion 
of  the  widely  distributed  group  of  hysterics,  so  that,  upon  accurate  investiga- 
tion of  the  history  of  most  hysterics,  the  report  is  obtained  that  in  early  youth 
they  had  been  anemic. 

This  fact  bears  further  testimony,  in  my  opinion,  to  the  close  relationship 
of  chlorosis  and  hysteria.     Indeed  it  may  be  observed  in  various  realms  of 


TREATMENT  339 

hematology  that  diseases  of  the  blood  and  of  the  nervous  system  present  many 
identical  etiologic  factors,  and  frequently  show  a  certain  parallelism  in  their 
course. 

Finally,  the  fact  must  be  borne  in  mind  that  in  many  cases  chlorosis  appears 
as  a  hereditary  condition,  and  we  may  assume  that  both  the  debility  of  the 
nervous  system,  and  the  anatomical  incompleteness  in  the  structure  of  the 
vascular  system  are  inherited.  But  the  view  may  be  just  as  well  maintained 
that  errors  in  bringing  up  which  furor  the  outbreak  of  chlorosis  may  be  trans- 
mitted from  tin-  mother  to  the  daughter  in  consequence  of  the  faulty  manner 
of  life  in  some  families  just  as  a  disease  may  be  transmitted. 

PROGNOSIS 

The  prognosis  in  general  is  that  of  other  benign  diseases  which  are  readily 
cured,  and  consequently  it  may  in  general  be  regarded  as  favorable  from  the 
onset  It  is  especially  so  in  the  case  of  those  girls  in  whom  the  symptoms  have 
appeared  suddenly,  and  who  previously  neither  were  anemic  nor  showed  other 
pathological  symptoms.  Such  cases  occur  in  dome-tie-  who  have  grown  up 
in  the  country  or  in  a  small  town.  More  unfavorable  are  the  conditions  in 
girls  who  from  early  youth  have  shown  the  signs  of  anemia,  who  are  addicted 
to  all  the  previously  mentioned  errors  of  education  and  general  hygiene,  the 
importance  of  which  in  the  development  of  the  disease  has  been  indicated 
above.  Those  cases  arc  doubtless  particularly  unfavorable  that  are  complicated 
by  the  existence  of  anatomical  anomalies  of  the  heart  and  vascular  system 
such  as  were  pointed  out.  These  latter  young  girls,  in  consequence  of  their 
generally  lessened  power  of  resistance,  are  in  greater  danger  when  acute  dis- 
eases such  as  pulmonary  inflammations,  influenza,  enteric  fiver,  etc.,  appear 
inter  currently. 

TREATMENT 

Chlorosis  is  generally  amenable  to  treatment,  but  from  the  onset  we  must 
bear  in  mind  the  factors  which  favor  the  development  of  the  disease,  and  as 
every  rational  treatment  must  begin  by  an  attempt  to  remove  the  cause  of  the 
malady,  or  at  least  it-  predisposing  element-,  it  becomes  the  duty  of  the  physi- 
cian to  try  to  discover  in  the  individual  case  what  causes  have  favored  the 
development  of  chlorosis,  a  point  that  is  of  paramount  importance  in  family 
practice,  when'  the  error  mu-t  be  Bought  in  the  general  mode  of  life  of  the 
family  and  particularly  in  the  bringing  up  of  young  girls.  This  is  often  a 
difficult  and  delicate  task,  and  requires  great  tact  and  judgment  on  the  part 
of  the  physician. 

Particularly  for  this  reason,  i.e.,  because  the  development  of  the  disease 
is  favored  by  the  injudicious  manner  of  life  and  habits  of  the  family,  it  is 
wi-c  in  many  cases  to  n  move  the  patient  from  her  usual  surroundings  and 
place  her  in  a  suitable  sanatorium,  preferably  in  a  suitable  health  resort;  in 
many  cases  the  results  will  prove  that  stubborn  cases  of  chlorosis  that  have 

resisted  all   the  therapeutic  efforts  of  home  practice  are  -p lily  cured  on 

removal   from  their  former  Burroundines.     It   mav  be  maintained  with  cer- 


340  CHLOROSIS 

tainty  to-day  tliat  there  is  no  specific  in  the  treatment  of  chlorosis,  and  that 
even  iron,  which  Felix  Xiemeyer  declared  in  his  time  to  be  a  specific,  cannot 
be  looked  upon  as  such  nor  infallible. 

On  the  contrary,  experience  proves  that  some  chlorotics,  who  have  shown 
no  appreciable  improvement  under  a  plentiful  iron  treatment  because  their 
general  hygienic  surroundings  were  unchanged,  are  restored  to  health  in  a 
short  time  if  they — as  is  frequently  the  case,  for  example,  with  the  previously 
mentioned  domestics — are  sent  from  their  usual  sphere  of  activity  to  the 
country  where  fresh  air  and  generally  favorable  hygienic  conditions  exert  a 
curative  influence  upon  them  without  a  drug  therapy  of  any  kind  whatsoever. 

In  keeping  with  my  view  that  chlorosis  is  a  neurosis  in  which  the  blood 
alteration  is  not  the  essential  part  of  the  disease,  but  usually  forms  the  most 
constant  symptom,  I  have  for  some  time  attempted  to  influence  this  disease 
without  administering  drugs  that  have  a  specific  action  upon  the  blood  com- 
position, and  particularly  without  the  employment  of  iron  preparations,  but 
purely  by  the  same  dietetic  and  hydrotherapeutic  measures  which  are  em- 
ployed in  other  neuroses,  especially  in  hysteria.  With  this  antinervous  regime 
I  have  completely  cured  a  number  of  chlorotics  in  about  the  same  time  as  with 
the  ordinary  iron  therapy,  yet  it  is  true  that  some  individual  cases  were  favor- 
ably affected  after  an  iron  therapy  had  been  instituted. 

It  is  evident,  at  all  events,  that  under  hospital  treatment  with  good  nurs- 
ing and  proper  nutrition,  -the  use  of  sweat  baths  at  the  beginning,  friction 
with  light  massage  later,  and  the  internal  administration  of  some  nervines 
such  as  bromide  or  valerian,  but  without  any  iron  medication,  the  same  favor- 
able results  can  be  obtained  as  are  observed  in  girls  who  regain  their  health  by 
being  sent  back  to  their  country  homes. 

This  therapeutic  experience  strengthens  my  belief  in  the  view  that  chloro- 
sis is  a  peculiar  neurosis  going  hand  in  hand  with  a  damage  in  hemoglobin 
formation,  and,  to  my  surprise,  I  recently  found  that  Sydenham  in  his  excel- 
lent "  Lectures  upon  Hysteria,"  which  even  to-day  are  well  worth  reading, 
particularly  emphasizes  this,  that  chlorosis  is  curable  by  the  same  remedies 
which  are  effective  in  hysteria. 

In  spite  of  these  experiences,  I  do  not  by  any  means  intend  to  deny  the 
value  of  iron  treatment  in  chlorosis.  This  has  been  demonstrated  in  prac- 
tice, time  and  again,  by  numerous  examples;  I  generally  advise  the  adminis- 
tration of  iron  in  the  treatment  of  chlorosis.  I  merely  wish  to  point  out  that 
in  these  cases  iron  is  not  to  be  looked  lipon  as  a  specific,  that  we  must  not 
commit  the  error  of  thinking  that  enough  is  done  when  we  prescribe  a  good 
iron  preparation  for  a  chlorotic  girl,  but  that  the  main  point  in  treatment 
undoubtedly  consists  in  good  nursing  and  diet. 

Tbe  treatment  of  chlorosis  is  best  begun  by  ordering  complete  rest  in  bed, 
a  laxative  to  relieve  the  coprostasis,  and  something  to  stimulate  the  appetite. 
It  is  well  at  the  start  to  ascertain  by  an  examination  of  the  gastric  contents 
the  state  of  the  secretory  and  motor  functions  of  the  stomach ;  for,  in  some 
cases,  as  has  been  stated,  hydrochloric  acid  is  in  excess,  while  in  others  it  is 
diminished,  and  in  still  other  cases  atony  of  the  gastric  walls  exists  which 
prevents  the  timely  expulsion  of  the  ingesta.     All  of  these  morbid  changes 


TREATMENT  341 

in  the  stomach  must  be  relieved  by  a  rational  treatment  before  we  proceed 
with  a  special  therapy;  and.  as  a  rule,  it  is  comparatively  easy  to  correct  these 
anomalies  of  secretion. 

The  diet  in  the  beginning  must  consist  of  easily  digested  food,  of  which 
milk  is  of  the  greatest  importance,  and  only  in  very  stout  girls  is  it  necessary 
to  limit  or  entirely  withhold  this,  the  best  nutritive  measure.  Easily  digested 
vegetables,  especially  the  green  vegetables,  such  as  spinach,  which,  by  the  way, 
contains  a  small  amount  of  iron,  green  peas  and  beans,  mashed  potatoes,  and 
rice  are  particularly  advisable.  Later  on,  finely  scraped  raw  beef  or  scraped 
ham  may  be  allowed,  while  the  use  of  e^^^,  at  least  in  large  amounts,  is  not 
recommended  on  account  of  the  intestinal  decomposition  which  readily  ensues. 
Very  frequently  at  the  onset  of  treatment  it  i-  necessary  to  remove  the 
edematous  swellings  which  appear  in  the  face,  giving  the  patient  a  peculiar 
puffy  appearance;  these  are  also  seen  in  the  ankles  and  elsewhere.  For  this 
purpose,  venesection  has  lately  been  employed  again,  as  it  was  by  many  physi- 
cians at  the  beginning  of  the  preceding  century,  though  even  then,  when 
venesection  was  in  vogue,  experienced  physicians  such  as  Becquere]  and  Kodier, 
on  the  basis  of  their  exact  blood  investigations,  cautioned  the  profession  against 
the  indiscriminate  employment  of  venesection  in  chlorosis.  To-day,  with  our 
knowledge  of  the  more  minute  constituents  of  the  blood  in  chlorosis,  vene- 
section cannot  he  looked  upon  as  a  justifiable  therapeutic  measure;  for  the 
plethora,  i.e.,  the  excessive  accumulation  of  fluid  in  the  blood,  the  removal 
of  which  was  attempted  by  the  exponent-  of  the  venesection  therapy,  is  rather 
increased  by  the  Id—  of  blood  and  by  the  consequent  inflow  of  lymph,  and  in 
my  opinion  the  only  favorable  result  of  venesection  i-  the  reactive  outbreak  of 
Sweat  to  which  these  physicians  attached  great   weight. 

This  effect  of  the  outbreak  of  sweat  upon  the  fluid  accumulated  in  the 
blood  and  in  the  tissues  ean.  in  my  opinion,  lie  brought  about  more  effectively 
and  with  less  danger  by  "  simple  sweat  bath.  In  puffy  chlorotic-,  during  the 
first  period  of  l  he  treatment,  I  employ  hoi  baths  followed  by  sweating  two  or 
ihne  linns  a  week,  and  1  lind  that  the  subjective  difficulties  a-  well  as  the 
objective  findings  are  always  favorably  influenced  thereby. 

Massage,  too.  i-  effective,  particularly  a-  long  a-  the  patient-  remain  in 
bed;  it  acts  very  favorably  in  stimulating  the  circulation  and  the  entire 
metabolism. 

Iron  lh< zrapy,  as  already  mentioned,  forms  an  essential  adjuvant  in  the 
treatment  of  chlorosis,  although  to-day  we  no  longer  hold  the  old  opinion  that 
iron  is  directly  utilized  in  the  formation  of  hemoglobin  in  the  body,  but  it  i- 
to  be  looked  upon  inainlv  as  "  stimulant  fur  the  hematopoietic  organs.  That 
iron  actually  reaches  the  fluids  of  the  body  by  absorption,  a  point  that  ha-  been 
questioned  even  very  recently,  has  Lately  been  positively  proven  chiefly  by 
the  invesl igations  of  Quincke. 

The  cumber  of  iron  preparations  at  our  disposal  foT  therapeutic  purposes 
i-  exceedingly  huge.  Besides  the  inorganic  compound-  of  iron  such  a-  ferrum 
oxy datum,  ferrum  sulphuricum,  ferrum  citricum,  ferrum  carbonicum,  ferrum 
chloratum,  «ml  ferrum  sesquichloratum,  we  possess  countless  newer  prepara- 
tions which  contain  iron  in  albumin  combinations,  and  to  these  lately  have 


342  CHLOROSIS 

been  added  remedies  which  contain  hemoglobin  itself  in  different  combina- 
tions. 

All  of  the  last-named  remedies  are  based  upon  the  hypothesis  that  iron  is 
absorbed  and  assimilated  more  readily  when  combined  with  albumin  products, 
especially  those  prepared  from  blood  itself  in  accordance  with  modern  organo- 
therapy ;  these  give  to  the  organism  as  directly  as  possible  a  compensation  for 
the  loss  of  hemoglobin  in  the  pathologically  altered  blood. 

Of  the  organic  iron  preparations  there  are  to  be  named  fcrratin,  an  arti- 
ficially produced  iron  preparation  (Schmiedeberg),  which  is  said  to  be  iden- 
tical with  the  iron  combinations  present  in  the  organism  and  in  the  food; 
further,  ferrum  peptonatum  and  the  various  liquores  ferri  albuminati.  Of 
iron-containing  blood  preparations  new  ones  are  combined  and  placed  upon  the 
market  almost  daily,  so  that  it  is  scarcely  worth  while  to  mention  the  names 
of  these,  for  the  most  part,  ephemeral  preparations.  Especially  fashionable 
in  practice  are  hematogen.  hemaldumin.  hemol.  sanguinal.  etc.  It  must  be 
remembered  in  the  employment  of  all  these  remedies  that  in  all  probability 
the  iron,  whether  given  in  an  organic  or  inorganic  combination,  is  primarily 
attacked  by  the  gastric  juice  and  changed  into  a  chlorid  combination,  and  that 
later  it  is  absorbed  in  the  bowel  as  an  iron  chlorid  albuminate.  It  is  therefore 
quite  unlikely  that  the  artificial  or  natural  iron  albuminates  are  absorbed  in 
the  form  in  which  they  are  administered,  and  it  may  be  assumed  that,  during 
the  time  of  their  absorption  into  the  fluids  of  the  body,  great  labor  is  thrown 
upon  the  stomach  and  intestine,  much  greater  than  in  the  administration  of 
inorganic  preparations. 

Eegarding  the  special  activity  of  these  remedies  in  chlorosis,  neither  from 
literature  nor  from  my  own  experience  are  many  observations  of  patients  of 
this  sort  known  to  me,  from  which  it  might  be  concluded  with  any  certainty 
that  any  one  of  the  above-mentioned  organic  preparations  produces  a  cure 
more  rapidly  and  with  greater  certainty  than  is  observed  upon  the  administra- 
tion of  the  ordinary  iron  preparations. 

What  is  particularly  lauded  by  the  manufacturers  concerning  these  reme- 
dies is  the  useful  action  of  the  albumin  contained  in  them ;  but  it  must  be 
mentioned  that  these  amounts  of  albumin  are  so  small  that  they  play  no  role 
in  the  nutrition  of  the  chlorotic,  particularly  as  in  this  disease  there  is  no 
noteworthy  deficiency  in  albumin  metabolism. 

Unquestionably  the  majority  of  these  modern  remedies  act  by  suggestion, 
and  therefore  in  practice  we  can  rarely  do  without  them,  as  the  laity  nowadays 
manifest  the  greatest  interest  in  the  products  of  pharmaceutical  industry.  In 
cases,  however,  in  which  the  therapy  remains  uninfluenced  by  these  subjective 
effects  upon  the  patient,  as  in  hospital  treatment,  there  is  absolutely  no  reason 
for  rejecting  the  old  well-tried  iron  preparations  in  their  various  combinations ; 
thus,  for  example,  the  excellent  Blaud's  pills. 

According  to  the  suggestion  of  C.  Gerhardt,  for  some  years  I  employed 
with  success  liquor  ferri  sesquichlorati,  three  to  five  drops  three  times  daily, 
diluted  in  water. 

The  numerous  iron  springs  in  Germany  and  neighboring  countries  contain 
iron  for  the  most  part  as  a  suboxid  combined  with  carbonic  acid,  and  the 


PROPHYLAXIS  343 

waters  are,  therefore,  suitable  for  drinking  at  the  spring;  not,  however,  for 
bottling,  as  carbonic  acid  readily  passes  off  and  the  iron  is  then  precipitated. 
A  few  springs  contain  sulphate  of  iron,  and  still  fewer,  chlor  id  of  iron. 

The  best-known  German  iron  springs  are  in  Pyrmont  in  the  Duchy  of 
Waldeck,  Langenschwalbach  at  the  Taunus,  Booklet  (near  Kissingen),  Char- 
lottenbrunn, Cudowa  and  Flinsberg  in  Silesia,  Driburg  in  the  Teutoburger 
Woods.  Elster  in  Saxony,  Franzensbad  in  Bohemia,  Kohlgrub  in  Bavaria,  900 
meters  above  the  sea,  Mushau  in  the  Lausitz.  Liebenstein  in  Meiningen,  Freien- 
walde on  the  Oder  in  Brandenburg,  Pulzin  in  Pomerania,  Reinerz,  500  meters 
high,  in  the  earldom  of  Glatz.  Steben  in  Upper  Franconia. 

Of  foreign  iron  springs  there  are  particularly  to  be  named:  Farnbühl  in 
Luzerne.  St.  Moritz  in  the  Upper  Engadine.  1,700  meters  above  the  sea,  and 
Val  Sinestra  in  the  Lower  Engadine;  further,  Haarlem  in  Holland,  Szlidcz 
in  Hungary.  Spa  in  Belgium. 

Besides  iron,  in  some  cases  arsenic  is  of  use  as  in  other  anemias;  and 
therefore,  besides  the  preparations  of  the  pharmacopeia,  arsenical  spring- 
waters  must  also  be  considered;  the  best  known  are  those  of  Roncegno  and 
Levico  in  the  Southern  Tyrol  as  well  as  the  Guber  Spring  in  Srebrenica  in 
Bosnia. 

The  beneficial  effect  of  all  of  these  iron  and  iron-arsenic  spring  cures  cer- 
tainly does  not  consist  only  in  their  contents  of  iron  and  arsenic,  but  quite 
as  much  in  the  stimulation  to  metabolism  by  change  of  climate  and  the  con- 
stant outdoor  life,  bo  that,  in  fact,  many  extremely  chlorotic  patients  are  seen 
to  recover  in  these  regions  who  .-how  but  slight  improvement  while  at  home  in 
spite  of  any  iron  preparation. 

Of  other  drugs  quinin  is  chiefly  to  be  mentioned,  while  remedies  such  as 
phosphorus,  manganese,  and  organopreparations,  for  example,  bone-marrow, 
thymus,  etc.,  are  of  no  importance. 

PROPHYLAXIS 

Although  in  the  direct  treatment  of  the  chlorotic  symptom-complex  a  great 
variety  of  dietetic,  physical  and  medicinal  auxiliary  remedies  are  at  our  dis- 
posal, it  iini-t  aevertheless  !><■  repeated  that  many  cases  of  chlorosis  belong  to 
ttic  diseases  which  are  readily  preventable,  ami  particularly  where  the  social 
position  of  young  girls  precludes  the  necessity  of  their  earning  their  own  live- 
lihood, and  the  external  conditions  an'  favorable  for  healthy  development. 

Since,  in  spite  of  thi-.  the  disease  is  observed  frequently  in  well-to-do 
families,  it  mu-t  he  attributed  wholly  /"  the  utter  Ignorance  even  to-day  in  the 
most  highly  cultured  families  regarding  //"■  fundamental  principles  of  hygiene, 
a  deplorable  condition  which  mu-t  be  combated,  on  the  one  hand,  by  a  greater 
dissemination  of  the  law-  of  hygiene  among  the  people,  and.  on  the  other  band, 

by  the  activity  of  each  individual   family  physician. 

It   is  Bufficienl   here,  to  avoid  repetition,  -imply  to  refer  to  the  deleterious 

factor-  which  have  I n  previously  mentioned  a-  predisposing,  and  which  may 

I»«-  removed  in  a  large  measure  by  hygienic  regulation  of  the  mode  of  life,  by 
bodily  exercise,  exercise  in  the  open  air.  etc 


LEUKEMIA 

By   W.    von    LEUBE,  Würzburg 

Since  the  discovery  of  leukemia  by  Virchow  in  1845,  we  designate  by  this 
term  a  disease  characterized  by  an  increase  in  the  number  of  white  cells  in  the 
blood  as  the  result  of  the  morbid  activity  of  the  blood-forming  organs,  and  in 
which  the  blood  alteration  forms  the  essential  feature  of  the  progressive  and 
pernicious  course  of  the  disease.  [The  blood  changes  dominate  the  clinical 
picture,  and  are  manifest  in  many  organs  post  mortem,  but  it  is  the  belief  of 
most  authorities  that  the  heightened  activity  of  glands  and  marrow  to  which 
they  are  due  is  itself  a  result  of  some  toxic  (chemotactic)  stimulus. — Ed.] 

This  definition  is  sufficient  clearly  to  differentiate  "leukocytosis"  from 
leukemia.  In  leukocytosis  we  are,  in  fact,  also  dealing  with  an  increase  of 
the  leukocytes  in  the  circulating  blood;  but  this  is  a  transitory  symptom  in  the 
course  of  manifold  diseases.  At  the  same,  leukocytosis  is  not,  like  leukemia, 
a  morbid  condition  of  a  progressive  and  pernicious  nature;  on  the  contrary 
it  is  in  a  measure  the  expression  of  the  self-protective  power  of  the  body 
against  the  disease  present. 

COMPOSITION   OF  THE   BLOOD 

Without  a  thorough  knowledge  of  the  composition  of  the  blood  and  of 
the  genesis  of  its  different  morphologic  elements,  an  insight  into  the  nature 
of  leukemia  is  impossible.  We  shall,  therefore,  describe  briefly  the  normal 
condition  of  the  blood  and  of  its  cellular  elements  before  we  discuss  leukemia 
in  detail.1 

The  three  formed  elements  of  the  blood  are,  as  is  generally  known,  the 
red  blood  cells,  the  white  blood  cells  and  the  blood-plaques.  These  last  have 
thus  far  little,  or  no,  importance  in  pathology. 

The  red  blood  cells,  "  erythrocytes,"  are  flat,  circular,  biconcave  discs, 
averaging  7.5  micromillimeters  in  diameter.  Normally  they  do  not  contain 
a  nucleus,  but  consist  of  a  protoplasmic  stroma  the  gaps  of  which  are  filled  with 
hemoglobin.  The  formation  of  the  red  blood-corpuscles  occurs  in  embryonic 
as  well  as  in  post-fetal  life  from  nucleus-containing,  colored  blood  cells,  the 

1  This  article  relating  to  the  diagnosis  and  pathogenesis  of  leukemia  is  based,  in  the 
main,  upon  the  complete  and  recently  revised  chapter  on  Leukemia  in  the  sixth  edition 
of  my  "Special  Diagnosis  of  Internal  Diseases"  (English  edition,  Leube-Salinger,  D. 
Appleton  &  Co.,  1904.) 

344 


COMPOSITION  OF  THE  BLOOD  345 

hematoblasts.  These  cells  are  invariably  present  in  the  red  bone-marrow  of 
the  flat  bones,  of  the  sternum  and  of  the  ribs,  the  base  of  the  skull  and  the 
vertebras.  The  red  blood  cells  which  at  first  contain  a  nucleus,  lose  this  later 
by  caryolysis,  i.e.,  by  dissolution  of  the  nucleus  (according  to  some  investi- 
gating authors  by  expulsion)  and  then  enter  the  circulating  blood  as  non- 
nucleated  red  blood-discs.  We  must  at  present  adhere  to  the  view  that  in 
post-fetal  life  the  red  (non-nucleated)  blood  cells  are  formed  exclusively  in 
the  red  bone-marrow,  namely,  from  the  nucleus-containing,  red  blood  cells 
which  are  constantly  present  in  these  regions.  The  latter  cells,  the  hemato- 
blasts, appear,  at  least  in  embryonic  life,  to  arise  from  lymphocytes  by  hemo- 
globin production,  first  as  megaloblasts,  which  perhaps  are  originally  the 
mother  cells  of  the  normoblasts.  [Several  authorities  of  the  first  rank  take 
exception  to  this  account  of  the  hematoblasts,  and  believe  that  red  and  white 
cells  arise  from  different  stems. — Ed.]  However,  after  the  latter  have  been 
formed,  they  increase  by  mitosis,  constantly  producing  new  normoblasts.  Be- 
sides the  bone-marrow,  in  embryonic  life  the  lymph-glands  also  probably  have 
an  erythropoietic  function  [probably  also  the  liver,  and  possibly  the  spleen. — 
Ed.];  but  in  the  adult  organism  blood-formation  occurs  only  in  the  bone- 
marrow,  where  also  the  transformation  of  normoblasts  into  non-nucleated  blood 
discs  occurs  (by  caryolysis).  Under  normal  conditions  only  non-nucleated 
blood  cells  pass  from  the  bone-marrow  into  the  blood.  Whenever  an  appre- 
ciable quantity  of  nucleated  red  blood  cells  is  found  in  the  blood,  pathological 
conditions  are  present:  Infections,  intoxications,  inanition.  If  large  num- 
bers of  nucleated  blood  cells  are  in  circulation,  severe  anemias,  even  of  the 
severest  character,  are  present. 

When  the  red  blood  cells  die  they  are  replaced  by  fresh  material  coming 
from  the  bone-marrow,  so  that  the  number  of  erythrocytes  remains  at  almost 
a  constant  figure,  namely,  about  5,000,000  for  men  and  about  4,500.000  for 
women  to  the  cubic  millimeter,  a  proportion  of  about  600  to  1  of  the  white  cells 
[5,000,000  is  too  low  for  the  average  of  healthy  adnlt  males  in  America.  The 
•  "iicct  figure  is  much  nearer  6,000,000. — Ed.]  The  majority  of  the  blood 
cells,  unquestionably,  disintegrate  in  the  liver.  We  are  justified  in  this  as- 
sumption for  reasons  which  need  not  be  here  minutely  considered,  and  of 
which  only  one  shall  be  mentioned,  viz.,  that  in  the  liver  Large  amounts  of 
biliary  coloring  matter  are  daily  produced.  But  bile,  as  its  chemical  compo- 
sition proves  (hematin  C82H82N404Fe  by  taking  up  water  and  giving  off  iron — 
-f-  2H20  —  Fe — forms  bilirubin  C82l  L,.\'  ,<  >,., ).  can  only  consist  of  hemoglobin 
which  has  been  given  up  from  the  stroma  of  the  red  blood  cells.  We  can  in 
fact  artificially  increase  at  will  the  production  of  biliary  coloring  matter  by 
the  injection  of  hemoglobin  into  the  blood. 

The  white  blood  cells  (leukocytes)  represent  colorless,  membraneless  cells 

with   one  or  more  nuclei  and   a   protoplasm    variously   constituted.      Since   the 

introduction  of  new  methods  of  staining  in  examining  the  blood,  the  firsl 
application  and  completion  of  which  we  owe  to  P.  Ehrlich'a  excellent  investi- 
gations in  the  pathology  of  the  blood,  the  fact  has  developed  that  normal  blood 

contains  not  only  two  varieties  of  leukocytes,  aa  wraa  assumed  for  a  long  time, 
but  many  kinds,  differing  markedly  from  each  other.     It   i-  besl   to  differen- 


346  LEUKEMIA 

tiate  two  principal  varieties,  mononuclear  and  polynuclear   (or  polymorpho- 
nuclear) cells,  both  of  which  show  various  sub  varieties : 

A.  Mononuclear  Forms  :  Cells  with  one  nucleus  and  varying  amounts 
of  basophilic,  non-granular  protoplasm. 

1.  Lymphocytes,  characterized  by  a  large,  round,  centrally-placed  nucleus 
and  a  narrow  protoplasmic  ring.  The  latter,  as  well  as  the  nucleus,  reacts 
basophil  ically,  especially  the  protoplasm  which  shows  no  granulations.  [No 
granulations,  that  is,  with  Ehrlich's  stain.  With  the  Romanowsky  stain  a 
variety  of  pink,  violet,  and  sometimes  a  few  blue  granules  are  seen  in  the 
protoplasm  of  the  lymphocytes.  This  is  true  of  all  sizes  of  lymphocytes, 
though  commoner  in  the  large  forms. — Ed.]  Tbe  lymphocytes  have  no  power 
of  ameboid  movement.  [I  am  convinced  by  the  observations  of  several  com- 
petent men  that  lymphocytes  (especially,  but  not  only,  the  larger  forms)  do 
have  the  power  of  ameboid  movement. — Ed.]  The  majority  of  them  scarcely 
attain  the  size  of  the  red  blood  discs;  rarely  are  large  lymphocytes  found,  espe- 
cially in  the  blood  of  children.  The  number  of  lymphocytes  amounts  to  about 
25  per  cent,  of  the  white  blood-corpuscles.  Some  individual  examples,  espe- 
cially of  the  larger  forms,  show  slight  segmentation  of  protoplasm.  2.  Large 
mononuclear  leukocytes,  twice  or  three  times  larger  than  the  lymphocytes, 
differing  markedly  from  the  large  lymphocytes,  in  that  the  large,  usually  oval 
nucleus  is  generally  eccentrically  situated  and  that  the  non-granulated  proto- 
plasm is  relatively  well  developed.  This  protoplasm  and  the  nucleus  have, 
like  the  lymphocytes,  a  basophilic  reaction,  but,  in  contrast  to  the  latter,  the 
protoplasm  stains  less  readily  than  the  nucleus.  Transitional  forms  between 
the  first  and  second  variety  are  not  observed,  and  for  this  reason,  according 
to  Ehrlich,  the  "  large  mononuclear  "  cells  are  strictly  differentiated  from  the 
lymphocytes,  all  the  more  so  as  "  transitional  forms  "  from  the  large  mono- 
nuclear to  the  polynuclear  are  observed,  i.  e.,  large  cells  with  neutrophilic 
granulation  and  with  indentations  in  the  nucleus.  [All  recent  and  unpreju- 
diced observers  seem  to  me  to  agree  that  there  are  abundant  transitional  forms 
between  the  "  large  lymphocyte  "  as  here  described  and  the  "  large  mononu- 
clear leukocyte  "  of  the  same  text.  A  differentiation  of  these  two  varieties  is 
in  my  opinion  impossible. — Ed.]  The  number  of  the  large  mononuclears  in 
normal  blood  is  always  small  (about  one  per  cent.). 

B.  Polynuclear  Forms:  Cells  with  several  small  nuclei  or  usually  with 
a  polymorphous  nucleus,  i.  e.,  with  marked  indentations  of  the  nucleus,  so  that 
some  of  the  nuclear  segments  are  connected  by  thin  chromatin  threads.  Tbe 
polymorphonuclear  ("polynuclear")  leukocytes  are  further  characterized  by 
ameboid  movement.  The  protoplasm  is  granular  and  shows  varying  condi- 
tions regarding  staining  which  give  rise  to  the  differentiation  into  the  three 
following  varieties: 

1.  Neutrophilic  polynuclear  leukocytes,  usually  designated  as  "polyxra- 
clears,"  characterized  by  the  dense  granulation  of  the  protoplasm  and  the 
affinity  of  the  same  to  "  neutral  "  staining  material.  They  form  in  the  nor- 
mal blood  about  70  per  cent,  of  the  white  blood-corpuscles.  [There  are  no 
true  neutral  stains.  A  special  differential  acid  stain  like  Ehrlich's  "  triacid  " 
is  what  is  here  referred  to. 


COMPOSITION  OF  THE   BLOOD  347 

The  normal  percentage  of  polynuclear  leukocyte*  is  in  this  country  more 
often  near  60  per  cent,  than  near  70  per  cent. — Ed.] 

2.  Eosinophile  cells,  characterized  by  their  size  and  by  the  coarse  granules 
in  their  protoplasm  which  stain  intensely  by  acid  stains  (eosin).  [The  size  of 
eosinophiles  is  not  characteristic.  They  are  about  the  size  of  a  polvnuclear 
cell  or  often  a  little  smaller,  but  their  irregular  shape  (as  seen  in  thin  smear 
preparations)  renders  a  definite  statement  as  to  their  diameter  difficult. — 
Ed.]  They  resemble  the  neutrophilic  polvnuclear  cells  and,  like  these,  are 
markedly  contractile;  their  number  amounts  to  about  3  per  cent,  of  the  white 
blood-corpuscles. 

3.  Basophilic  leukocytes,  "'mast-cells''  are  scanty  in  normal  blood  (0.5 
per  cent,  of  the  leukocytes).  They  are  characterized  by  the  intense  basophilic 
reaction  of  the  granules  in  their  protoplasm  and  by  the  very  slight  staining 
affinities  of  the  nucleus;  the  granulation  does  not  color  with  the  triacid  stain, 
hence  mast-cells  appear  in  triacid  preparation-  as  light,  non-granular  cells. 

Opinions  are  more  at  variance  concerning  the  origin  of  the  white  blood- 
corpuscles  than  of  the  red.  although  a  number  of  investigators  (Virchow, 
K  oil  ike  i'.  Max  Schultze,  Neumann,  Heidenhain,  Arnold.  Mokoff,  Rieder, 
Engel  and.  above  all.  P.  Ehrlieh,  and  in  late  years  A-kanazy.  Pappenheim  and 
Rubenstein  )  have  closely  Btudied  this  subject.  At  present,  it  is  difficult,  almosl 
impossible,  to  take  a  positive  stand  in  the  mooted  question.  The  following 
theory  is  probably  more  in  accordance  with  present  opinions  than  any  other. 

After  the  investigations  of  the  last  decade,  and  especially  since  the  intro- 
duction id'  tinctorial  method-  of  examination  by  Ehrlich.  Virchow's  view  that 
the  lymphocytes  are  the  young,  the  leukocytes  the  old,  form-  of  tin;  cells,  the 
latter  arising  from  the  former,  can  no  longer  lie  accepted  in  it-  Bimple,  >trict 
conception.  On  the  contrary,  it  is  better  to  adhere  to  the  view  that  the  lympho- 
cytes, the  leukocytes  and  the  hemaglobin-containing  cell-  represenl  separate 
stages  of  developmenl  of  cell-,  which  probably  are  only  alike  in  their  first 
elements — namely,  cells  with  non-granular,  weakly  basophilic  protoplasm  and 
one  round  nucleus.  From  these  the  myelocytes  develop  in  the  bone-marrow, 
the  protoplasm  becoming  granular  (neutrophilic  or  eosinophilic),  while  tin1 
nucleus  -till  retains  its  pound  form;  in  the  later  -tage-  of  development  the 
granulation  becomes  more  marked,  the  nucleus  flattened,  -innate  and.  finally, 
pigmented  (polymorphonuclear  leukocytes  with  neutrophilic  or  eosinophilic 
reaction).  At  this  age  the  cells  enter  the  circulating  blood  as  "  polynuclear  ** 
leukocyte-.  A  U-w  immature  cells,  i.e..  still  basophilic,  non-granular  ami  Hip- 
plied  with  one  nucleii-.  enter  the  blood  as  the  so-called  "  mononuclear*'  leuko- 
cyte-, which  then  mature  in  the  blood,  becoming  polvnuclear  leukocytes.  The 
cell-   which   have   begun    to   mature   in   the   bone-marrow    remain    in   the  hon, - 

marrow  until  perfectly  mature,  becoming  polvnuclear  leukocytes,  bo  that  the 
blood  doe-  not  normally  contain  myelocytes.  The  mature  polynuclear  cell-, 
however,  enter  the  blood  upon  chemotactic,  physiological  irritation  in  rela- 
tively -mall  hut  usually  quite  constant  numbers,  under  pathological  condi- 
tion- frequently  in  very  large  numbers  ("leukocytosis").  The  loss  of  the 
polynuclear  cells  which  pa-s  into  the  blood  is  compensated  by  the  for- 
mation of  new  primary  stages  of  the  same,  the  myelocytes,  and  by  the  fur- 


348  LEUKEMIA 

fcher  development  of  the  latter  into  a  correspondingly  greater  number  of  poly- 
nuclear  cells. 

In  the  spleen  and  lymph-glands  leukocytes  are  not  produced,  at  least 
not  in  noteworthy  amounts  (even  in  cases  where  they  are  much  needed,  as  in 
leukocytosis).  On  the  other  hand,  the  lymph-glands  (the  spleen  only  to  a 
slighter  degree)  are  the  points  of  origin  for  the  formation  of  lymphocytes, 
which,  as  is  well  known,  represent  one-fourth  of  the  white  blood  cells  in  nor- 
mal blood.  Similarly  to  the  myelocytes  they  are  probably  also  formed  in  the 
bone-marrow  from  large  basophilic,  mononuclear  cells  which  are  the  early 
stages  of  the  leukocytes  and  generally  do  not  enter  the  blood,  or  at  most  only 
as  "  large  lymphocytes "  in  children,  and  under  pathologic  conditions  in 
lymphatic  leukemia  (where  they  are  met  with  in  the  blood  in  great  numbers, 
particularly  in  the  acute  form  of  the  disease).  Just  as  the  myelocytes  mature 
("age")  into  polymorphonuclear  leukocytes,  so  does  the  nucleus  of  the 
lymphocytes  pass  through  this  aging  process  in  that  it  later  undergoes  lobula- 
tion and  fragmentation  (Bieder' s  cells),  without  the  protoplasm  losing  its 
basophilic,  non-granular  character. 

The  nuclear  changes — lobulation  and  segmentation  into  several  nuclei — 
therefore,  indicate  the  physiological  age  of  the  cells;  just  so  may  we  assume, 
in  general,  that  a  slighter  staining  quality  (amblychromasia),  especially  of 
the  cell  nuclei,  characterizes  the  cells  as  incomplete,  undeveloped,  in  contrast 
to  the  intensely  staining  ("  trachy chromatic  ")  mature  forms. 

As  already  mentioned,  the  bone-marrow  is  almost  exclusively  the  organ  of 
production  of  the  myelocytes  and  polynuclear  cells,  although  typical  myelo- 
cytes are  found  in  the  spleen  and  lymph-glands  (without  having  been  carried 
in  by  the  blood  stream).  On  the  other  hand,  the  lymph-glands  are  to  be  con- 
sidered the  seat  of  production  of  the  small  lymphocytes.  Of  course,  we  find 
lymphocytes  in  scant  numbers  in  the  bone-marrow  too ;  of  these  it  is  probable 
that  a  fair  proportion  have  been  carried  in,  a  part,  however,  having  been 
formed  in  the  marrow  itself. 

The  origin  of  the  very  small  number  of  mast-cells,  which,  under  normal 
conditions,  are  found  in  the  blood,  has  not  yet  been  determined  with  certainty. 
Most  investigators  assume  that  they  originate  in  the  connective  tissue;  others 
believe  that  they  develop  from  lymphocytes. 

SYMPTOMS   AND   BLOOD-CHANGES 

Let  us  now  return  to  the  discussion  of  leukemia.  Marked  cases  are  mani- 
fest at  the  first  glance  by  the  extreme  pallor  of  the  patient's  skin  and  mucous 
membranes,  and  occasionally  by  the  color  of  the  blood  as  obtained  by  puncture 
or  incision  of  the  finger  tips  which  may  be  whitish  red.  [Cases  are  pale  only 
if  anemia  has  developed,  and  this  even  in  well-marked  cases  is  often  not  nota- 
ble. In  the  later  stage  of  the  disease,  but  not  until  then,  anemia  becomes 
severe. — Ed.]  The  microscopic  examination  of  the  fresh  blood  in  cases  of 
leukemia  of  high  grade  shows  even  without  counting  the  abnormal  increase 
in  the  white  blood-corpuscles.  But  a  count  and  a  comparison  with  the  num- 
ber of  erythrocytes  is  absolutely  necessary  in  the  less  marked  cases.     Whereas 


SYMPTOMS  AND  BLOOD-CHANGES  349 

normally  we  find  an  average  of  8,000  leukocytes  (in  children  somewhat  more, 
9,000  to  10,000)  in  a  cubic  millimeter  of  the  blood  taken  from  the  veins,  i.  e., 
one  white  cell  to  600  erythrocytes,  the  number  of  leukocytes  may  bo  increase 
in  leukemia  that  the  proportion  is  1  to  50,  1  to  L0,  or  1  to  2.  In  fact,  the  red 
and  wbite  blood-corpuscles  may  even  be  present  in  similar  amounts  in  the 
blood.  The  count  of  white  blood-corpuscles  shows  100,000  and  even  500,000 
and  more,  to  the  cubic  millimeter. 

In  some  cases  of  leukemia,  no  noteworthy  change  in  the  erythrocytes,  either 
in  number  or  appearance,  occurs;  as  a  ruh1,  however,  they  are  decreased  in 
numbers  to  about  one-half  of  the  normal  or  even  Less,  just  as  in  severe  anemias. 
In  general  the  decrease  of  the  erythrocytes  is  in  proportion  to  the  increase 
in  the  number  of  white  blood-corpuscleg;  But  the  numerical  relation  of  the 
erythrocytes  in  leukemia  is  a  secondary  consideration,  and  the  diagnosis  of 
the  affection  depends  primarily  upon  the  white  blood-corpuscles.  There  are 
cases  of  simple  anemia  in  which  the  number  of  red  blood-corpuscles  is  mark- 
edly diminished,  but  the  production  of  white  has  remained  normal  :  then  the 
proportion  of  the  white  to  the  red  cells  may  become  1  to  25,  etc.,  without 
leukemia  being  present.  For  example,  in  pernicious  anemia,  with  a  diminu- 
tion of  the  erythrocytes  to  250,000  to  the  cubic  millimeter,  and  a  normal  con- 
dition of  the  white  blood  cells  (8,000),  the  proportion  would  be  about  1  to 
30  and  still  no  leukemia  would  be  present.  Leukemia  is.  however,  to  be  as- 
sumed under  all  circumstances  if  the  proportion  falls  below  l  to  20,  because 
these  figures  can  only  occur  when,  besides  the  decrease  in  the  number  of  the 
red  blood-corpuscles  a-  a  result  of  anemia  (even  in  the  most  excessive  diminu- 
tion of  the  Bame  that  has  been  observed  up  to  the  present  in  cases  of  per- 
nicious anemia),  the  number  of  Leukocytes  is  absolutely  increased  at  the 
same  time. 

Besides  the  diminution  in  the  number  of  red  blood-corpuscles,  tin1  blood 
also  contain-,  as  a  rule,  numerous  nucleated  red  blood-corpuscles  in  the  form 
of  normoblasts,  more  rarely  megaloblasts,  or  transitional  form-  between  the-.'. 
The  amount  of  hemoglobin  in  the  blood  is  diminished  in  leukemia  but  the 
coloring  of  the  Individual  corpuscles  (abnormally  decreased  in  numbers)  need 
not  be  diminished.  An  increase  in  the  blood-plaques  ha-  also  been  observed 
upon  several  occasions. 

The  diagnosis  of  leukemia  can  be  made  «without  further  consideration  in 
eases  which  -how  an  extraordinary  increase  of  the  white  blood-corpuscles,  but 
in  doubtful  cases  the  presence  of  the  disease  can  only  be  determined  by  an 
exact  microscopical  examination  of  the  morphology  of  the  leukocytes. 

Besides  the  increase  in  the  white  cells,  what  i-  particularly  conspicuous  in 
the  microscopic  examination  of  leukemic  blood  i-  thai  in  the  majority  of  cases 
(be  polynuclear  cell-  are  most  numerous;  in  other  cases,  however,  the  Lympho- 
cytes form  (he  greater  number,  and  tin'-  type  of  blood  alteration  persists  dur- 
ing the  entire  course  of  the  illness.  |  In  l!  cases  of  myelogenous  leukemia 
studied  by  me  the  polynuclear  cell-  average  L7.5  per  cent.  It  i-  the  polymor- 
phous condition  of  the  blood,  the  endless  variety  among  the  Leukocyte  forms, 
that  mo-t  impresses  one  in  this  disease.— Ed.]  We.  therefore,  quite  properly 
differentiate  two  different  varieties  of  leukemia. 


350  LEUKEMIA 

1.  Lymphocyte  leukemia. 

2.  Leukocyte  leukemia. 

Since  the  source  of  the  lymphocytes,  as  has  been  mentioned,  is  the  spleen 
and  the  lymph-glands,  and  that  of  the  leukocytes  is  the  bone-marrow,  the 
common  designations  of  lymphatic  leukemia  (lymphemia)  and  myelogenous 
leukemia  (myelemia)  may  be  selected  for  these  two  basic  forms  of  leukemia. 
As,  however,  the  bone-marrow  also  normally  produces  typical  lymphocytes. 
and  as  it  has  been  determined  in  rare  cases  that  an  over-flooding  of  the  blood 
with  lymphocytes  may  occur  by  proliferative  changes  in  the  marrow  without  en- 
largement of  the  spleen  and  lymph-glands  (myelogenous  lymphemia),  I  pre- 
fer the  less  prejudicial  division  of  the  leukemic  forms  into  "  lymphocyte  leu- 
kemia "  and  "  leukocyte  leukemia." 

In  the  blood  at  the  autopsy,  or  after  prolonged  standing  of  the  blood  of 
leukemics,  Charcot's  crystals  are  found,  usually  within  the  leukocytes,  and  par- 
ticularly in  the  eosinophilic  polynuclear  cells.  Their  relation  to  the  last- 
named  cells  has  lately  been  determined  beyond  doubt,  so  that  we  may  say: 
Wherever  eosinophile  cells  are  present  in  large  numbers,  Charcot's  crystals  are 
also  found.  This  at  once  makes  it  clear  that  they  are  absent  in  lymphocyte 
leukemia,  and,  on  the  other  hand,  that  the  crystals  are  not  only  found  in  leuko- 
cyte leukemia  but  in  all  diseases  in  which  eosinophiles  occur  in  large  numbers, 
nasal  polypi,  bronchial  asthma,  etc.  The  demonstration  of  Charcot's  crystals 
is,  therefore,  by  no  means  pathognomonic  of  leukemia,  the  less  so  as  they  are 
also  found  in  normal  bone-marrow,  which  is  not  to  be  wondered  at. 

In  comparison  with  the  results  of  the  microscopic  examination  of  the 
blood,  all  the  other  morbid  phenomena  of  leukemia  are  of  decidedly  subordi- 
nate importance,  even  though  in  the  individual  case  they  greatly  aid  in  the 
diagnosis.  There  are  cases  of  leukemia  in  which,  besides  the  alteration  in 
the  blood  and  the  symptoms  of  anemia  in  connection  therewith,  all  other 
objectively  demonstrable  morbid  phenomena  are  absent,  and  the  diagnosis  must 
be  made  entirely  from  the  blood  findings !  These  are,  however,  under  all 
circumstances,  as  will  be  shown  later,  rare  and  exceptional  cases ;  the  rule  is 
that  many  organs,  especially  those  connected  with  blood-formation,  suffer 
marked  changes  which  may  be  demonstrated  by  physical  examination. 

In  this  connection  we  must  mention  particularly  the  enlargement  of  the 
spleen  which  is  present  in  the  majority  of  cases  of  leukemia.  The  splenic 
tumor  is  usually  of  considerable  size;  it  extends  to  the  median  line  or  beyond 
and  downward  to  the  hypogastric  region.  On  account  of  its  sharp  indented 
margin,  the  direction  of  the  growth  of  the  tumor,  and  especially  its  evident 
origin  from  the  left  hvpochondrium,  there  is  rarely  cause  to  doubt  that  we  are 
dealing  with  a  tumor  of  the  spleen.  The  diagnosis  may  be  difficult  if,  as  in 
one  of  my  cases,  the  large  spleen  turns  so  that  the  hilus  appears  at  the  top. 
The  consistence  of  the  splenic  tumor  is  hard ;  its  circumference,  after  it  has 
attained  a  certain  size,  is  usually  constant.  Rarely  transient  shrinkages  are 
noted,  or,  on  the  other  hand,  excessive  swelling  or  rupture  of  the  organ.  As 
a  rule  the  swollen  spleen  is  not  sensitive  to  palpation,  and  the  subjective  diffi- 
culties which  the  tumor  causes  are  generally  slight.  At  most  the  patients 
complain  of  a  feeling  of  fulness  in  the  abdomen  and  slight  difficulty  in  respira- 


SYMPTOMS  AXD  BLOOD-CHAXGES  351 

tion;  less  frequently  pain  occurs  in  the  -picnic  region,  or  oven  inflammatory 
phenomena  which  manifest  themselves  in  peritoneal  friction  sounds  in  this  area. 

In  some  of  the  eases,  most  frequently  in  lymphocyte  Leukemia,  lymph- 
gland  enlargement  occurs.  [1  have  never  -ecu  lymph-gland  enlargement  ex- 
cept in  lymphocyte  leukemia. — Ed.]  As  a  rule,  the  glands  of  the  neck  and 
axillary  region,  more  rarely  those  in  other  areas  of  the  periphery  or  the  inter- 
nal lymph-glands,  are  affected.  The  glandular  tumors  are  moderately  hard, 
the  skin  covering  them  is  movable  and  not  reddened.  If  the  mesenteric  and 
retroperitoneal  gland-  are  hyperplastic,  they  may  be  occasionally  felt  through 
the  abdominal  walls.  In  case  the  enlargement  affects  the  tracheal  and  bron- 
chial lymph-gland.-,  at  least  a  probable  diagnosis  of  this  result  of  the  leukemia 
may  be  made,  provided  the  symptoms  of  tracheal  or  bronchial  stenosis,  of 
paralysis  of  the  vocal  cords,  the  result  of  pressure  upon  the  recurrent  laryn- 
geal nerve,  or  difficulty  in  deglutition,  arise.  In  marked  cases  of  swelling 
of  the  tracheo-bronchial  lymph-glands  or  of  the  persisting  thymus  gland,  the 
percussion  note  over  the  manubrium  is  dull  and  the  bone  i-  arched  outward. 
In  the  adenoid  tissue  of  the  tonsils  and  also  in  the  adenoid  follicles  at  the  root 
of  the  tongue  hyperplasia  and  swelling  may  likewise  be  noted. 

Besides  the  spleen,  the  various  lymph-glands,  and  the  other  adenoid  organ-, 
the  bone-marrow  is  almost  always  affected  |>y  anatomical  change-.  Accord- 
ing to  the  experience-  gathered  up  to  this  time,  changes  in  the  hone-marrow 
are  invariably  present  in  leukemia.  In  lymphocyte  leukemia  we  find,  espe- 
cially in  the  lymph-glands,  in  the  spleen  and  eventually  in  the  liver,  but 
invariably  also  in  the  bone-marrow,  proliferations  of  the  lymphoid  tissue, 
which  in  these  cases  may  become  so  plentiful  that  the  production  of  the  poly- 
nuclear  cells  in  the  hone-marrow  and  the  passage  of  the  same  into  the  blood 
may  be  prevented  by  the  overgrowth  of  the  lymphocyte-  in  the  marrow.  A- 
30011  as  the  lymphocytes  begin  to  enter  the  blood,  floating  in  from  the  bone- 
marrow,  hyperplastic  lymph-glands  and  spleen  (quite  passively  as  we  must 
assume  From  Ehrlich's  convincing  deduction-),  the  picture  of  lymphocyte  leu- 
kemia develops. 

The  implication  of  the  hone-marrow  in  the  leukemic  processes  can  never 
be  determined  with  certainty  intra  vitam  by  the  sensitiveness  of  the  hone  to 
pressure,  but  only  when  the  microscopic  examination  reveals  in  the  circulating 
blood  mononuclear,  granular  marrow  cells,  the  origin  of  which  from  the  hone- 
marrow  i-  certain,  and  also  large  quantities  of  nucleated  red  blood  cells. 

Besides  the  three  above-named  organs  which  are  particularly  affected  in 
leukemia,  other  portion-  of  the  body,  although  Less  frequently,  are  involved  in 
changes  which  are  in  direct  relation  to  Leukemia.  In  the  majority  of  i 
the  liver,  in  consequence  of  Leukemic-cell  infiltration  between  the  acini.  Is 
enlarged.  The  Burface  is  smooth,  it-  consistence  moderately  hard.  Harked 
grades  of  ascites  and  jaundice  arc  only  to  be  expected  if  the  periportal  lymph- 
glands  are  enlarged  and  press  upon  the  portal  vein  and  biliary  passages.  As- 
cites, that    i-.  the  transudation  of  a  large  amount  id'  fluid   into  the  peritoneal 

cavity,  may  also  be  caused  by  a  leukemic  nodular  infiltration  of  the  peritoneal 
layers  and  of  the  omentum.     This  i-,  however,  not  frequent. 

Leukemic  infiltrations  occur  also  in  the  stomach  <ni<l  intestine;  they  arise 


352  LEUKEMIA 

from  adenoid  tissue  areas  of  the  wall  (i.  e.,  the  solitary  follicles).  Dyspeptic 
phenomena  and  diarrhea  point  to  this  complication  but  do  not  permit  cer- 
tainty in  diagnosis.  In  some  patients  a  leukemic  stomatitis  and  pharyngitis 
develop. 

It  is  noteworthy  that,  in  spite  of  the  diminution  of  the  erythrocytes,  nei- 
ther dyspnea  nor  orthopnea  occurs  in  leukemia,  at  least  not  according  to  my 
experience  (provided  there  are  no  complications  on  the  part  of  the  respiratory 
organs).  [I  have  repeatedly  seen  dyspnea  and  even  orthopnea  in  leukemia  as 
soon  as  anemia  became  severe  or  circulatory  stasis  marked. — Ed.]  Petten- 
kofer  and  Voit  first  demonstrated  in  one  of  their  patients,  who  was  suffering 
from  leukemia,  the  ability  of  the  organism,  during  rest,  regardless  of  the 
diminution  of  the  erythrocytes,  to  assimilate  as  much  oxygen  as  a  healthy 
person  with  the  same  nourishment.  Neither  do  marked  disturbances  of 
metabolism  occur  in  the  course  of  leukemia,  or,  if  they  are  now  and  then 
noted,  they  are  at  least  not  dependent  upon  the  leukemic  processes  as  such. 
The  tendency  of  the  leukemic  to  catarrhal  affections  of  the  respiratory  passages 
may  favor  the  production  of  pulmonary  inflammation  in  some  cases ;  in  other 
cases  lymphatic  infiltrations  form  in  the  lungs.  The  development  of  lym- 
phatic nodules  has  been  noted  in  the  epiglottis,  in  the  larynx  and  in  the 
trachea,  also  upon  the  pleura ;  not  rarely  do  transudates  appear  in  the  pleural 
cavity. 

Painful  non-ulcerating  nodes  occasionally  develop  in  the  skin,  and  must 
be  looked  upon  as  leukemic  lymphoid  formations.  [Deafness  was  produced  in 
one  of  my  cases  by  nodules  in  the  ear. — Ed.]  A  tendency  to  profuse  sweat- 
ing is  not  rare,  and  adds  to  the  exhaustion  of  the  patients. 

The  murmurs  noted  upon  auscultation  of  the  heart  are  of  an  accidental 
nature,  the  result  of  the  marked  anemia  which  occurs  in  leukemia.  [Late 
in  the  course  of  the  disease. — Ed.]  In  consequence  of  poor  nutrition  and 
exhaustion  of  the  heart  muscle  such  a  dilatation  of  the  heart  may  occur  that 
the  valves  though  still  normal  in  their  length  can  no  longer  close.  Thus  rela- 
tive mitral  and  tricuspid  insufficiency  may  develop. 

Xot  only  such  relative  cardiac  insufficiencies  and  accidental  murmurs  may 
occur  as  a  consequence  of  the  anemia  which  develops  in  leukemia,  but  also 
quite  a  number  of  other  symptoms  such  as  appear  more  or  less  regularly  in 
any  anemia;  e.g.,  palpitation,  weakness  and  lassitude,  vertigo,  headache, 
attacks  of  syncope,  and  edema;  perhaps  also  fever  which  is  irregular  but  may 
be  at  times  quite  high  (102°  F.  to  104°  F.). 

In  the  course  of  leukemia,  in  rare  cases,  long-continued  priapism  occurs, 
due  perhaps  to  a  thrombosis  in  the  corpora  cavernosa.  This  symptom  lias 
been  observed  a  number  of  times,  and  occurs  so  rarely  in  other  conditions 
that  its  presence  should  be  considered  suggestive  of  leukemia. 

Of  special  interest  in  the  diagnosis  of  leukemia  are  the  changes  in  the  eye- 
ground  which  occur  in  the  course  of  the  affection.  In  keeping  with  the  in- 
creased number  of  white  corpuscles  and  the  anemia  the  fundus  of  the  eye 
has  an  unusual,  pale,  orange-yellow  appearance.  But  this  discoloration  is  not 
conspicuous  in  all  cases;  it  is  always  absent  if  the  amount  of  hemoglobin  has 
not  been  materially  decreased.     The  so-called  retinitis  leuhemica  is  character- 


SYMPTOMS  AND  BLOOD-CHANGES  353 

ized  by  an  extremely  tortuous  condition  of  the  veins,  a  band-like  opacity  of 
the  retina,  and  hemorrhages  into  the  same,  as  well  as  by  opacity,  indistinct 
contours  and  bluish-yellow  color  of  the  optic  nerve  papilla.  Xot  rarely  the 
veins  are  accompanied  by  white  streaks,  and  white  areas  intermixed  with  hem- 
orrhages  are  visible  in  the  macula;  the  hemorrhages  are  circular  in  shape, 
with  a  prominent  yellowish-white  center.  Occasionally  there  is  a  tendency  to 
the  development  of  numerous  large  hemorrhages  which  may  also  occur  in  the 
vitreous  body,  so  that  the  ophthalmoscopic  picture  may  resemble  that  of 
thrombosis  of  the  central  vein  of  the  retina.  Such  a  thrombosis  may  occur 
simultaneously  with  hemorrhages  around  the  optic  nerve  and  in  the  latter 
itself,  and  may  also  develop  in  the  orbital  portion  of  the  optic  nerve.  Func- 
tional disturbances  are  present  to  only  a  slight  extent. 

The  changes  in  Ihr  urine  observed  in  leukemia  are  of  great  importance 
in  diagnosis,  as  well  as  in  the  study  of  the  disease. 

Apart  from  the  occasionally  observed  albuminuria,  which  is  in  part  the 
resull  of  the  anemia,  in  pari  the  consequence  of  lymphomatous  infiltration  of 
the  renal  substance  (which  is  indicated  by  the  presence  of  easts  and  of  a  large 
number  of  leukocytes  in  the  sedimeni  of  the  urine),  a  change  in  the  excretion 
of  the  solid  constituents  of  the  urine  is  more  or  less  frequently  found  in  leu- 
kemia. An  absolute  and  relative  increase  of  the  excretion  of  uric  acid  (up  to 
8  grams  per  diem)  has  been  almost  invariably  observed. 

This  increase  of  uric  acid  in  leukemia  is  certainly  not.  as  was  formerly 
supposed,  the  result  of  insufficient  oxidation  in  the  organism.  This  opinion 
is  contradicted  not  only  by  the  results  of  the  investigations  of  IVttenkofer  and 
Voit,  but  also  by  the  fact  determined  by  Stadthagen,  that  in  the  body  of  the 
patient  suffering  from  leukemia  the  sodium  urate  which  has  been  administered 
per  OS  is  capable  of  further  oxidation.  Neither  can  the  excessive  production 
of  uric  acid  be  considered  due  to  the  enlargement  of  the  spleen  commonly 
present  in  Leukemia,  as  patients  with  chronic  splenic  tumor  excrete  uric  acid 
in  normal  amounts  in  contrast  to  leukemia  with  enlargement  of  the  spleen, 
in  which  the  excretion  of  uric  acid  is  markedly  increased.  As  we  know  now 
thai  uric  acid  originates  from  the  nuclein  which  is  liberated  in  the  decompo- 
sition of  the  cellular  nuclei,  especially  by  oxidation  of  alloxur  bases  which  are 
contained  in  aucleinic  acid,  the  conclusion  is  obvious  that  the  increase  of  uric 
acid  excretion  in  the  course  of  Leukemia  may  be  referred  to  the  destruction  of 
a  relatively  greater  number  of  leukocytes  than  under  normal  conditions.  How- 
ever, the  increased  excretion  of  uric  acid  may  also  be  an  expression  of  in- 
creased  function,  that  is,  of  metabolism  of  the  superfluous  leukocytes,  bo  that 
an  increase  of  uric  acid  excretion  in  the  course  of  leukemia  is  by  no  means  a 
proof  of  greal  decomposition  of  leukocytes  and  their  nuclei. 

The  excretion   of   urea   u-uallv  doc-   not    differ   from    the   normal:   in    two 

cases  of  severe  Leukemic  cachexia  in  my  clinic  Fleischer  and  Penzoldl  noted 
an  increase  of  area  excretion,  hut  this  was  in  the  Late  stages  of  leukemia,  when, 
as  in  carcinomatous  cachexia,  a  marked  decomposition  of  organic  albumin 

with  increase  of  fl scretion  of  nitrogen  occur-.     Hematuria  is  also  observed 

in  the  course  of  Leukemia. 

This  symptom  is  connected  with  the  general  hemorrhagic  diathesis  of  the 
24 


354  LEUKEMIA 

leukemic,  one  of  the  most  important  symptoms  of  leukemia  as  regards  diag- 
nosis, and  especially  as  regards  prognosis.  Hemorrhages  may  occur  in  the 
urinary  passages  and  in  various  parts  of  the  body,  i.e.,  in  the  respiratory  pas- 
sages, in  the  digestive  tract,  in  the  skin  (purpura),  in  the  subcutaneous  con- 
nective tissue  (sometimes  in  the  form  of  colossal  hemorrhagic  tumors),  in  the 
muscles,  in  the  internal  parts  of  the  ear,  etc. ;  hemorrhages  are  also  noted 
in  the  central  nervous  system  in  the  course  of  leukemia,  and  may  give  rise  to 
apoplectic  attacks  with  paralysis,  or  they  may  result  in  sudden  death;  these 
intercurrent  hemorrhages  are  usually  the  cause  of  the  fatal  outcome  of  leu- 
kemia, or,  at  least,  they  predispose  to  it.  Multiple  effusions  of  blood  occa- 
sionally occur  in  the  peripheral  nervous  system,  in  the  sheaths  of  the  nerves 
or  in  the  nerves  themselves,  and  these  result  in  fatty  degeneration  of  the  nerves 
and  the  muscles  supplied  by  them,  in  some  cases  of  leukemia  the  hemorrhagic 
diathesis  may  so  dominate  the  clinical  picture  that  the  cases  appear  to  be 
purpura  hemorrhagica  until  the  examination  of  the  blood  discloses  the  error. 
[This  is  especially  true  of  the  cases  of  acute  lymphatic  leukemia. — Ed.] 

The  symptoms  of  leukemia — the  increase  in  the  number  of  leukocytes  in 
the  blood  as  well  as  the  enlargement  of  the  spleen  and  lymph-glands — may  for 
a  time  ameliorate  greatly  in  the  course  of  intercurrent  infectious  diseases. 
[Or  even  without  any  known  cause.  Some  of  these  spontaneous  remissions 
happen  to  coincide  with  the  inception  of  a  special  method  of  treatment  and 
lead  to  the  reports  of  curative  drugs,  etc. 

Of  the  remissions  under  X-ray  treatment,  mention  will  be  made  later. 
—Ed.] 

The  classification  generally  in  vogue  until  lately  by  which  individual  cases 
of  leukemia  were  grouped  as  "  myelogenous  "  or  as  "  lymphatic  "  leukemias, 
according  as  the  spleen  or  the  lymph-glands  were  enlarged,  can  no  longer  be 
maintained  from  a  hematological  standpoint,  chiefly  because  of  the  impor- 
tant researches  of  Neumann  and  Ehrlich.  For  some  time  we  differentiated 
not  only  between  splenic  and  lymphatic  leukemias,  but  also  between  cases  of 
the  splenic-medullary  variety,  or  those  of  the  pure  medullary  form  ("  myeloge- 
nous leukemia  ").  But  these  designations  for  the  individual  varieties  of  leu- 
kemia, based  as  they  are  on  the  changes  prominent  in  the  clinical  picture  in 
organs  more  or  less  implicated  in  the  formation  of  the  blood,  are  not  justified 
either  from  a  hematological  or  from  a  clinical  standpoint.  For,  in  both 
forms,  the  lienal  and  the  lymphatic,  the  bone-marrow  is  primarily  implicated 
in  the  changes  of  the  hematopoietic  process,  and,  on  the  other  hand,  the  char- 
acteristic blood  picture,  which  in  one  case  may  show  a  marked  preponderance 
of  lymphocytes,  in  another  a  great  majority  of  leukocytes  and  their  primary 
stage-,  is  usually  not  at  all  altered,  whether  the  lymph-glands  or  the  spleen 
are  enlarged  or  not.  We  therefore  recur  to  my  chosen  differentiation  of  only 
two  varieties,  according  to  the  point  of  origin  of  the  cell  forms  which  are 
markedly  increased  in  the  blood — lymphocyte  leukemia  and  leukocyte  leu- 
Ire  min.  The  differentio-diagnostic  points  of  these  two  varieties  of  leukemia 
are  the  following : 

1.  Lymphocyte  Leukemia.  The  blood  picture  is  characterized  by  a  con- 
spicuous preponderance  of  large  and  small  lymphocytes  in  comparison  to  the 


SYMPTOMS   AND  BLOOD-CHANGES  355 

leukocytes.  Nucleated  red  blood  cells  and  megaloblasts,  although  found  in 
the  blood  in  lymphocyte  leukemia,  yet,  compared  with  their  usual  abundance 
in  leukocyte  leukemia,  are  by  uo  means  prominent. 

According  to  the  course  of  the  affection,  two  varieties  must  be  differen- 
tiated, the  acute  and  the  chronic. 

Acute  lymphocyte  leukemia  ("acute  lymphemia"),  the  recognition  of 
which  we  owe  above  all  to  Ebstein  and  A.  Fraenkel,  is  characterized  by  its 
rapid,  often  febrile,  course,  resembling  a  severe  infectious  disease.  Besides  the 
usually  Insignificant  enlargemenl  of  the  spleen  and  lymph-glands,  the  other 
clinical  phenomena  of  leukemia  are  present,  stomatitis,  retinitis,  etc.  Mosi 
prominent  in  the  clinical  picture  is  the  hemorrhagic  diathesis,  so  thai  the 
affection  has  the  appearance  of  purpura  hemorrhagica  and  may  be  confounded 
with  tlii-.  all  the  more  so  as  the  hemorrhages  occasionally  occur  before  the 
characteristic  blood  picture  of  acute  lymphemia  is  formed.  The  Mood  picture 
itself  is  highly  characteristic:  Preponderance  of  the  lymphocytes,  especially 
of  the  large  one-,  very  rarely  of  the  -mailer,  with  a  vesicle-like,  sometimes 
deeply  indented  nucleus;  erythroblasts  are  present  although  few  in  num- 
ber; the  polynuclear  cells  are  not  only  relatively  but  also  absolutely  decreased. 
The  number  of  white  blood  cells  compared  to  the  red  ones  may  be  extraordi- 
narily -rent  (up  to  1  to  1  !).  [In  the  majority  of  cases,  however,  it  is  not 
3siv< — much  less  than  in  myelogenous  cases. — Ed.]  The  affection  may 
terminate  fatally  in  a  I'rw  days  or  a  U-w  weeks. 

Chronic  lymphocyte  leukemia  is  differentiated  from  the  above-described 
form  by  it-  greatly  protracted  course:  Gradual  enlargement  of  the  lymph- 
glands,  especially  those  of  the  neck,  also  enlargement  of  the  spleen  to  a  greater 
or  less  extent.  In  rare  cases,  even  in  a  very  chronic  course  (in  one  case 
under  my  observatiou  the  affection  lasted  at  leasl  two  years),  only  insignificant 
enlargements  of  the  glands  appear.  The  lymphoid  hyperplasia  of  the  hone- 
marrow  is  present  here,  as  in  the  acute  form.  The  hemorrhagic  diathesis  is 
also  quite  marked  in  the  chronic  form  of  leukemia,  and  as  consequences  of 
anemia  there  mav  be  a  -rent  variety  of  symptom-,  such  as  dilatation  and 
insufficiency  of  the  heart,  etc.,  which  may  threaten  life.  The  blood  picture 
in  the  main  resembles  that  of  the  acute  form,  i.e.,  mononuclear  lymphocytes, 
hut  usually  the  small  form-  are  mosl  prominent,  whereas  the  other  colorless 
blood  cell-  are  almost  absent.  Large  lymphocyte-  are  also  found  in  chronic 
lymphocyte  leukemia  during  the  entire  course  of  the  affection,  and  in  rare 
cases,  a-  in  the  acute  form,  they  mav  even  dominate  the  blood  picture. 

2.  I.i.i  ko<  vn  leukemia,  by  far  Ihr  most  frequent  form  of  leukemia,  may 
be  easily  differentiated  from  both  of  the  last-mentioned  varieties  of  leukemia  by 
it-  entirely  different  blood  picture.  The  increase  of  the  white  Mood  cells  is 
usually  very  marked;  here,  however,  the  polymorphonuclear  leukocytes  are 
greatly  increased  in  the  microscopic  picture:  neutrophils,  and.  above  all. 
eosinophilic  polynuclear  cell-  are,  a-  Ehrlich  ha-  found,  always  <ii>sniutrlij  in- 
creased. There  i-  invariably  an  absolute  increase  of  the  mast-cells  which  o 
-ionallv  are  twice  a-  numerous  a-  the  eosinophiles,  and  their  determination  is 
.,r  grea!  importance  in  a  diagnostic  respecl  because  a  marked  increase  of  the 
mast-cells  i-  onlj  observed  in  leukemia.     [The  absence  of  mast-cells  was  i 


356  LEUKEMIA 

cially  noted  in  3  of  my  41  cases. — Ed.]  The  phenomenon,  however,  which 
especially  characterizes  leukocyte  leukemia,  and  shows  its  origin  to  be  the 
changes  in  the  bone-marrow  ("myelogenous  leukemia"),  is  that,  besides  the 
polynuclear  cells,  their  ancestors,  the  mononuclear  granular  leukocytes,  i.  e., 
the  neutrophilic  and  eosinophilic  myelocytes,  are  always  found  in  the  blood 
and  occasionally  are  found  in  such  great  numbers  (up  to  100,000  per  c.mm.) 
as  to  simulate  at  first  sight  the  blood  picture  of  acute  lymphemia  with  its 
large  mononuclear  cells;  some  of  the  myelocytes  show,  as  has  already  been 
stated,  coarse  eosinophilic  granules  (eosinophilic  myelocytes).  The  cells 
which  have  been  described,  the  polynuclear  cells  as  well  as  the  mononuclear, 
are  occasionally  large,  at  other  times  remarkably  small  ("dwarf  forms"). 
Besides  these  immature  leukocytes  (the  myelocytes),  which  normally  are  not 
met  with  in  the  circulating  blood,  other  immature  forms  of  erythrocytes  also 
originating  in  the  bone-marrow  are  found  in  the  circulating  blood  stream  of 
patients  with  leukocyte  leukemia,  such  as  normoblasts  and,  more  rarely, 
megaloblasts  in  varying  amounts,  at  times  in  great  numbers. 

The  enlargement  of  the  spleen  in  this  variety  is  especially  well  marked, 
the  enlargement  of  the  lymph-glands  is  sometimes  quite  prominent,  at  other 
times  less  so.  [See  editorial  note  on  page  351. — Ed.]  It  is  remarkable  that 
we  rarely  have  an  opportunity  to  observe  the  development  of  the  tumors  step 
by  step.  Usually  the  physician  sees  the  disease  in  its  full  intensity,  so  that 
we  must  assume  that  leukocyte  leukemia  rapidly  reaches  the  acme  of  its  devel- 
opment. Besides  the  splenic  tumor  and  the  enlargement  of  the  glands,  the 
other  clinical  phenomena  have  already  been  fully  described :  The  hemorrhagic 
diathesis,  the  retinitis,  the  increase  of  uric  acid  in  the  urine,  etc. 

From  an  etiological  standpoint  there  is  little  of  value  in  the  diagnosis  of 
leukemia.  In  some  cases  leukemia  appears  to  follow  infectious  diseases  (ma- 
laria, diphtheria,  the  puerperium,  influenza,  etc.),  or  occurs  in  connection  with 
trauma,  as  concussions  (perhaps  especially  of  the  bones).  These  "causes" 
of  leukemia,  considered  as  direct  agents  producing  the  disease,  are  of  very 
questionable  nature.  This,  therefore,  justified  the  sensation  which  followed 
the  "discovery"  of  Löwit  (who  had  already  distinguished  himself  by  his 
studies  regarding  the  leukemic  process)  that  the  disease  was  due  to  the  pres- 
ence of  amcebse  in  the  blood  and  in  the  organs  producing  the  blood  cells.  In 
leukocyte  leukemia  Löwit  found  a  form  of  ameba  which  he  believed  to  increase 
in  the  blood  by  sporulation  (hamiamceba  leuca?miae  magna)  ;  in  lymphocyte 
leukemia  another  form  of  parasite  differing  from  the  former  by  its  active 
motility  (hsemamceba  leuc.  parva  vivax).  Doubtless  Löwit's  discovery,  if  con- 
firmed, would  be  of  the  greatest  value  in  the  explanation  of  the  nature  of  leu- 
kemia; but,  unfortunately,  we  cannot  as  yet  reckon  with  this  factor,  as  the 
investigations  are  by  no  means  concluded  and  have  called  forth  many  contra- 
dictory opinions.  [There  are,  I  think,  no  contradictory  opinions  among  those 
who  have  studied  Löwit's  preparations,  and  repeated  his  technic.  Competent 
observers  are  unanimous  in  believing  that  Löwit's  supposed  parasites  were,  in 
fact,  artefacts.     No  competent  investigator  has  confirmed  Löwit's  work. — Ed.] 

In  the  author's  opinion,  leukemia  is  due  to  a  specific  poison,  which  impairs 
the  process  of  blood  formation,  especially  that  of  the  white  blood  cells.     In 


SYMPTOMS  AND  BLOOD-CHANGES  357 

his  opinion,  the  important  question,  in  all  blood  diseases,  is  this:  What  kind  of 
poison  is  it  which  is  affecting  the  process  of  blood  formation  in  each  individual 
case .'     On  this  depend  the  changes  manifest  in  the  blood. 

1.  If  the  damage  chiefly  affects  the  red  blood  cells,  simple  "anemia"  re- 
sults, in  which  the  erythrocytes  deviate  more  or  less  from  the  normal  in  their 
number,  shape,  maturity  and  hemoglobin  percentage,  while  the  white  corpus- 
cles are  affected  only  incidentally,  and  especially  as  to  their  number. 

2.  If  the  poison  affects  chiefly  the  process  of  generation  of  the  white  cor- 
puscles, so  that  their  number  is  increased  and  their  morpbotie  relation  i- 
pathologically  altered,  the  blood  disease  presents  itself  in  the  form  of  a  leu- 
kemia. 

3.  If  the  damage  affects  all  components  of  the  blood  equally,  blood  dis- 
eases result  that  represent  a  complete  upsetting  of  the  process  of  blood  forma- 
tion with  changes  in  the  number  and  form  of  both  the  white  and  the  red  blood 
cells — blood  diseases  usually  described  as  transitional  or  mixed  forms  of  per- 
nicious anemia  and  leukemia.  It  is  difficult  to  classify  satisfactorily  the 
individual  cases  of  this  group  as  anemia  or  leukemia,  if  the  usual  terms. 
anemia  and  leukemia,  are  used  as  mutually  exclusive.  I  believe,  therefore, 
that  it  is  advisable  to  give  them  a  special  name,  for  instance,  "leukanemia  *' 
or  something  similar.1 

In  this  form  of  blood  disease,  as  already  remarked,  the  production  of  red 
and  white  blood-corpuscles  is  wholly  upset,  and  accordingly,  in  the  blood  pic- 
ture, decided  changes  appear  in  the  leukocytes  as  well  as  in  the  erythrocytes, 
such  changes  as  we  are  accustomed  to  note,  on  the  one  hand  in  Leukemia,  and  on 
the  other  hand  in  pernicious  anemia.  Blood  formation  may  cease  entirely, 
and  this  deficiency  can  no  longer  be  compensated  in  any  manner,  so  that  the 
organism  soon  succumbs  to  the  pernicious  blood  disease.  Clearly  to  illustrate 
the  affection  which  I  designate  as  leukanemia  I  shall  quote  the  complete  history 
of  a  case  observed  in  my  clinic: 

A  hoy.  K.  L.  aged  ten,  entered  the  hospital  May  6th,  and  died  May  9,  1900. 
Patienf  i-  said  to  have  been  always  weak,  but  never  Beriously  ill,  and  attended 
school  regularly  up  to  April  22d.  Mild  symptoms;  twice  vomiting  occurred, 
SO    that    the    patient    was    compelled    to    remain    at    home    from    April    22d    to 

April  29th.  On  April  29th  he  sang  as  a  choir  boy  in  church,  and  on  May  Isl 
again  attended  Bchool,  but  oe  May  5th,  on  account  of  his  pallor,  which  the 

i  In  my  opinion,  it  La  well  t<>  carry  <>iit.  in  the  main,  tlii-^  classification  of  blood 
diseases,  in  spite  of  the  fad  thai  in  typical  leukemias  not  only  normoblasts  are  found 
but  also  now  and  tlim  megaloblasts,  and  although,  vice  versa,  aparl  from  the  alterations 
in  the  differentia]  eounl  (the  predominance  of  lymphocytes),  a  few  myelocytes  are 
occasionally  found  in  seven  anemia».  Bui  these  findings  arc  of  subordinate  and  second- 
ary importance  compared  with  the  primary  condition,  according  to  which  the  'li- 
in  consonance  with  the  fundamental  principle  of  nosology  "a  potion  fial  denominatio," 
is  to  I»-  spoken  of  in  our  case  a>  leukemia,  in  another  as  anemia  gravis,  and  by  all 

diagnosticians  is  thus  commonly  designated.     A  di» sase  ean  only  receive  the  nan i 

"leukanemia"  when  both  leukocytes  and  erythrocytes  are  uniformly  and  decidedly 
damaged  in  their  development,  when  the  case  can  neither  be  pul  in  the  categorj  of 
leukemia  nor  in  thai  of  pernicious  anemia,  and  when  the  division  oi  blood  diseases  into 
two  groups  is  no  longer  possible* 


358  LEUKEMIA 

teacher  noticed,  he  was  sent  home.  From  May  3d  to  May  6th  he  still  took 
his  food  with  appetite;  then,  four  days  hefore  his  death,  epistaxis  occurred, 
with  yellow  discoloration  of  the  skin ;  pain  in  the  nape  of  the  neck  and  tooth- 
ache appeared,  as  well  as  pain  in  the  epigastrium.  In  the  course  of  the  day 
severe  apathy  became  more  and  more  noticeable,  increasing  to  complete  loss 
of  consciousness,  so  that  the  patient  was  brought  by  his  relatives  to  the  Julius 
Hospital. 

Status  praesens:  The  appearance  of  the  patient  denoted  serious  illness; 
skin  and  mucous  membranes  deathly  pale;  eyelids  and  hands  markedly  edema- 
tous; the  skin  over  the  rest  of  the  body  slightly  bloated,  showing  yellow 
discoloration  but  not  jaundice;  conjunctivas  snow-white.  Coma.  No  opis- 
thotonus, no  rigidity  of  the  neck  and  no  spasms.  Pupils  dilated,  reacting 
normally.  Liver  and  spleen  moderately  enlarged  and  hard;  sensitive  to  pres- 
sure. The  muscles  of  the  calves  of  the  legs  not  especially  sensitive  to  pressure, 
but  the  bones  of  the  thigh  as  well  as  the  sternum  extraordinarily  so.  Lungs 
normal.  The  cardiac  dulness  extended  to-  the  right  sternal  border;  heart 
sounds  clear;  gallop  rhythm,  undulation  of  the  veins  of  the  neck.  Urine 
contained  traces  of  albumin;  no  albumoses,  no  casts.  The  ophthalmoscopic 
examination  showed  feeble  filling  of  the  vessels,  especially  of  the  arteries, 
which  were  mere  threads — "  marantic  thrombosis  of  the  central  artery  with 
numerous  disseminated  hemorrhages."     Temperature  102°  F.  to  104°  F. 

As  the  symptoms  of  extraordinary  impoverishment  of  the  blood  were 
present,  besides  a  slight  enlargement  of  the  liver  and  spleen,  the  diagnosis 
was  set  down  as  "severe  anemia/'  On  account  of  the  edema  of  the  skin 
and  the  presence  of  albumin  in  the  urine,  a  nephritis  was  at  first  thought 
to  be  the  cause.  This  assumption,  however,  was  dropped  when  it  was  found 
that  only  traces  of  albumin,  but  neither  blood  cells  nor  epithelium,  nor  even 
casts,  were  present.  An  acute  infection  seemed  much  more  likely,  and  the 
rapid  course  of  the  disease,  the  severe  disturbance  of  the  general  condition, 
the  high  fever,  the  enlargement  of  liver  and  spleen  and  the  albuminuria  were 
in  favor  of  this.  Yet  the  clinical  picture  did  not  correspond  to  any  of  the 
usual  infectious  diseases.  It  was  obvious  that  only  an  exact  examination 
of  the  blood  would  clear  away  these  diagnostic  difficulties. 

The  blood  count  showed  an  excessive  diminution  in  the  number  of  eryth- 
rocytes: 256,000  per  c.mm. !  The  blood-corpuscles  varied  in  size  (with  some 
megalocytes),  and  the  triacid  stain  showed  that  some  red  corpuscles  contained 
nuclei:  Normoblasts  76,  megaloblasts  152,  in  a  c.mm.  The  .amount  of  hemo- 
globin of  the  entire  blood  was  not  more  than  10  per  cent.,  the  hemoglobin 
contents  of  the  individual  blood-corpuscles  (color-index)  was  therefore  rela- 
tively Increased. 

The  absolute  number  of  white  blood  cells  was  scarcely  increased,  10,fi00, 
though  when  compared  with  the  total  number  of  the  erythrocytes  it  seemed 
high.  1:24.  The  morphology  of  the  leukocyies  and  the  proportion  of  the 
individual  leukocyte  varieties  to  each  other  deviated  greatly  from  normal  con- 
ditions, so  thai  the  blood  picture  resembled  that  of  leukemic  blood.  Besides 
the  usual  neutrophilic,  polynuclear  leukocytes  which  were  present  in  dimin- 
ished amounts   (4,680),  many  myelocytes  were  seen   (1,380  neutrophils  and 


SYMPTOMS  AND  BLOOD-CHAN c  .1  s  359 

76  eosinophiles);  mast-cells  were  absent;  however,  there  were  large  mono- 
nuclear leukocytes  (228)  and  remarkably  numerous  lymphocytes  |  !.".'<j0), 
large  and  small — almost  as  many  as  polynuclear  cells.  Expressed  in  per- 
centage the  blood  contained:  Lymphocytes  40.2  per  cent,  (large  35.3  per  cent., 
small  4.9  per  cent.);  polynuclears  (neutrophilic  leukocytes)  11.1  per  cent.; 
myelocytes  13.6  per  cent,  (neutrophiles  13  per  cent.,  eosinophiles  0.6  per 
cent.);  large  mononuclear-  2.1  per  cent.;  and  but  very  few  mast-cells  (only 
one  found  in  all  the  blood  preparations  examined). 

The  course  of  the  affection  during  the  four  days  in  which  the  patient  was 
in  the  hospital  was  extraordinarily  rapid.  The  temperature,  which  varied 
between  102.2°  and  104°  F.  from  the  first  to  the  second  day.  dropped  on  the 
third  day  to  100.4°  P.,  falling  upon  the  fourth  day,  when  death  occurred,  to 
91.1°  F.;  consciousness,  which  had  been  lost  prior  to  his  admission  to  the 
hospital,  returned  on  the  second  day,  ami  continued  until  death.  The  energy 
of  the  heart,  however,  weakened  from  hour  to  hour.  The  cardiac  dulness, 
which  was  normal  at  the  onset,  became  more  and  mure  extended  without 
the  appearance  of  murmurs.  Weakness  increased  until  death  occurred  on 
May  9th. 

The  clinical  diagnosis  entered  at  the  Pathological  Institute  was;  "Pro- 
gressive pernicious  anemia,  enlargement  of  the  Liver  and  spleen,  infectious 
degenerative  processes  in  the  bone-marrow  with  disturbances  in  the  formation 
of  red  and  white  blood-corpuscles;  dilatation  of  the  heart,  myocarditis  (  ?)." 

The  main  points  in  the  autopsy  reporl  (v.  Rindfleisch)  may  be  mentioned 
as  follows:  Excessive  anemia  of  the  entire  body.  The  marrow  of  the  femin- 
in its  lower  half  everywhere  red.  that  of  the  sternum  reddish.  Spleen  some- 
what enlarged,  13.5  cm.  in  length,  8  cm.  in  breadth,  Z\  cm.  in  thickness:  upon 
section  lighter  than  normal,  consistence  somewhat  sofi  ;  Malpighian  bodies 
enlarged,  indistinct.  Liver  of  firm  consistence,  gives  a  distincl  amyloid  reac- 
tion, which,  however,  soon  disappears  when  the  organ  is  placed  in  water. 
The  heart  is  distinctly  dilated,  particularly  in  the  right  ventricle;  the  left  ven- 
tricle Bomewhat  Less  bo.  The  muscles  of  the  heart  are  very  anemic,  parts 
showing  grayish  discoloration  and  punctiform  hemorrhage-:  fatty  degenera- 
tion of  the  muscular  trabecular  in  the  Left  heart.  No  enlargement  or  change 
in  the  Lymph-glands.  Kidney-  pale,  in  part  showing  a  dappled  anemia: 
capsule  peels  easily;  consistence  somewhal  firmer  than  normal. 

The  anatomical  diagnosis  (v.  Rindfleisch)  was  as  follows :  Ancemia  maxima 
corporis  totius;  Hyperemia  ossium  cum  infiltratione  cellulari  partim  leuJco- 
cytica  partim  erythrocytica.  Lien  hyperplasticus  ex  intumescentia  leukocytica 
corpusculorum  Malpighii.  Hepar  modice  auctum  degeneratio  hepatis  amy- 
loidea.  Degeneratio  cordis  adiposa  praisertim  ventriculi  sinistri,  düatatio 
ventriculi  sinistri.     Myocarditis.     (Edema  pulmonis,  atelectasis. 

Microscopical  examination-;  (v.  Rindfleisch)  Bhowed:  In  the  spleen  areas 
of  Boftening,  in  the  internal  parts  of  which  were  abscess-like  accumulations 
of  polynuclear  cell-  hut  without  pyogenic  cocci:  a  softening  of  all  the  Mal- 
pighian bodies  with  transformation  of  their  lymphocyte-  into  pus  cell-.  Amy- 
loid degeneration  of  the  liver  not  affecting  the  interstitial  tissue  hut  merely 
the  liver  cell-  proper,  which  alone  gave  the  amyloid   reaction.     The  blood 


360  LEUKEMIA 

vessels  as  a  whole  were  free  from  amyloid  but  contained  numerous  detached 
large  myelocytes  besides  red  corpuscles.  As  a  curious  finding  may  be  men- 
tioned small  foci  of  liquefaction  about  one-fourth  the  diameter  of  an  acinus 
filled  exclusively  with  polynuclear  leukocytes  and  liver  cells  in  the  process 
of  gradual  dissolution,  but  containing  no  cocci.  These  foci  were  situated 
sometimes  near  the  edge  of  the  acinus,  sometimes  near  the  center,  and  were 
rarely  confluent.  No  siderosis  could  be  determined  in  several  examinations. 
The  heart  muscle  showed  fatty  degeneration  with  fragmentation  of  the  fatty 
muscle  fibers  and  hemorrhages  the  size  of  a  millimeter.  Kidneys  principally 
anemic.  The  bone-marrow  contained  chiefly  large  myelocytes  with  large  nu- 
clei, slightly  or  not  at  all  granular.  Normoblasts  were  found  mostly  around 
the  small  hemorrhages;  megaloblasts  were  more  scanty. 

Epicrisis. — The  blood  findings,  in  so  far  as  they  relate  to  the  red  blood- 
corpuscles  (250,000  erythrocytes,  76  normoblasts,  152  megaloblasts  in  a 
c.mm.),  would  class  this  affection  as  pernicious  anemia,  and  at  that  the  usual 
form — the  metaplastic — with  transition  of  the  yellow  bone-marrow  into  red, 
with  formation  of  profuse,  nucleated  red  blood-corpuscles,  and  especially  of 
megaloblasts  in  the  marrow,  and  their  entrance  into  the  circulating  blood. 
The  erythrocytes  were  relatively  rich  in  hemoglobin,  corresponding  to  the 
usual  finding  in  pernicious  anemia. 

The  condition  of  the  white  corpuscles  in  the  case  in  question  is  more 
important  than  that  of  the  red.  We  note,  point  for  point,  that  the  findings 
correspond  to  leukemic  blood,  yet  there  is  no  absolute  increase  worth  men- 
tioning in  the  white  blood  cells. 

The  great  number  of  myelocytes  in  the  blood  (and  also  in  the  bone- 
marrow)  is  primarily  conspicuous;  they  form  one-seventh  of  all  the  leuko- 
cytes. According  to  our  present  knowledge  of  the  genesis  of  the  leukocytes, 
myelocytes  may  be  looked  upon  as  the  product  of  blood  cell  formation  in  the 
hone-marrow ',  and  as  the  prior  stage  of  the  polynuclear  leukocytes  of  the  blood. 
It  can  hardly  be  disputed  that  in  our  case  the  transportation  into  the  blood 
of  these  immature  leukocytes  (the  mononuclear  neutrophilic  and  eosinophilic 
myelocytes)  represents  a  process  in  the  blood  analogous  to  the  emigration 
of  the  immature  erythrocytes,  the  normoblasts  and  the  megaloblasts.  This 
analogy  is  so  natural  that  the  question  may  well  arise  whether  this  condition 
— emigration  of  immature  leukocytes  with  the  simultaneous  emigration  of  the 
immature  erythrocytes  from  the  bone-marrow  into  the  blood — does  not  occur 
frequently  in  pernicious  anemia,  and  even  whether  it  does  not  invariably 
occur.  To  decide  this  question,  only  the  latest  investigations,  based  upon 
methods  of  staining  that  are  in  use  to-day,  should  be  considered.  From  re- 
searches which  are  in  this  respect  decisive  it  is  shown  that  the  appearance 
of  myelocytes  in  the  blood  of  patients  suffering  from  pernicious  anemia  is  not 
usual;  generally  none  or  apparently  but  few  (at  the  utmost  up  to  0.5  per 
cent.)  of  these  immature  leukocytes  are  found.  In  our  case,  however,  the 
blood  was  rich  in  myelocytes — they  represented  one-seventh  (!)  of  the  white 
blood  cells  and  the  one-hundred-and-eighty-fourth  part  of  all  the  blood  cells. 
We^must,  therefore,  assume  in  this  rare  case,  that  we  were  dealing  with  an 
insufficiency  in  the  function  of  the  bone-marrow,  affecting  simultaneously  the 


SYMPTOMS  AND  BLOOD-CHANGES  361 

formation  of  the  red  as  well  as  of  the  white  cells,  so  that  the  embryonic  forms 
of  the  red  and  white  cells  did  not  come  to  maturity.  These  cells,  i.  e.,  of  the 
(nucleated)  normoblasts  and  megaloblasts  as  well  as  of  the  myelocytes,  appear 
to  have  emigrated  into  the  blood  before  their  transformation  into  normal, 
finished  blood  cells  could  be  completed. 

Another  striking  feature  of  the  ease  was  that  (besides  the  neutrophilic 
or  eosinophilic  granular  myelocytes)  non-granular  myelocytes  and  even,  what 
is  more  conspicuous,  non-granular  polynuclear  cells  could  be  demonstrated 
with  certainty  in  the  circulating  blood — a  fact  that  may  perhaps  be  explained 
by  supposing  that  in  this  rapid  and  abbreviated  hematopoietic  process  not 
even  granulation  could  take  place,  much  less  complete  maturity  of  the  leuko- 
cyte forms  produced  in  the  bone-marrow. 

While  the  individual  points  in  the  blood  picture  of  our  case  which  have 
been  described  up  to  this  time  can  be  brought  into  genetic  connection  only 
with  a  severe  damage  in  the  function  of  the  bone-marrow,  this  source  of 
disturbance  of  the  blood  formation  is  questionable  because  of  the  remarkable 
relative  increase  of  the  lymphocytes  in  the  blood  (40  per  cent,  of  lymphocytes 
compared  with  -14  per  cent,  of  polynuclears) . 

We  might  at  first  suppose  the  latter  to  be  only  an  expression  of  the  mark- 
edly diminished  production  of  the  polynuclears  in  the  bone-marrow,  i.  e.,  a 
relative  increase  of  the  lymphocytes  because  the  formation  of  polynuclears  in 
the  bone-marrow  is  reduced,  while  that  of  the  lymphocytes  in  the  spleen  and 
lymph-glands  continues  unhindered — and  this  corresponds  to  the  important 
fact  which  Strauss  determined — the  relative  increase  of  the  lymphocytes  in 
pernicious  anemia.  The  circumstance  that  35  per  cent,  of  large,  and  only 
5  per  cent,  of  small,  forms  were  found  in  the  blood  is  opposed  to  this  view. 
Therefore  a  disturbance  in  the  formation  of  lymphocytes  musl  in  this  case 
be  assumed.  It  has  lately  been  regarded  as  certain  that  lymphocytes  are  nor- 
mally produced  not  only  in  the  spleen  and  in  the  lymph-glands  but  also  in 
the  bone-marrow;  hence  it  appears  rational  to  hold  the  damaged  function 
of  the  bone-marrow  responsible  also  for  the  disturbance  in  lymphocyte  forma- 
tion which,  in  our  ease,  no  doubt  existed.  But,  in  my  opinion,  this  is  im- 
possible, Bince  the  lymphocytes  in  the  bone-marrow,  examined  posl  mortem, 
wen-  MTv  few,  while,  in  contrast,  the  tissue  fluid  taken  from  the  spleen  one 
hour  after  death  contained  profuse  amounts  of  large  and  small  lymph-cells. 
It  appears  to  me,  therefore,  that  any  other  view  than  the  following  would  be 
forced,  namely,  that  the  increase  of  lymph-cells  in  the  blood  was  due  to  a 
greater  formation  of  these  cells  in  the  spleen.  This  idea  is  the  more  plausible 
since  the  lymph-glands  in  our  case  were  everywhere  absolutely  unchanged. 

The  results  of  the  analysis  in  this  case  may,  therefore,  be  summarized 
as  follows : 

A  simple  pernicious  anemia  was  not  present,  in  -pile  of  the  fact  that  tin1 
blood  showed  the  characteristic  changes  of  pernicious  anemia  in  the  hemoglo- 
bin-containing «ells  circulating  in  the  blood,  the  erythrocytes.  A.gains1  perni- 
cious anemia  was  the  enormous  production  of  myelocytes  and  their  transporta- 
tion into  the  blood,  the  scanty  presence  of  megaloblasts  in  the  bone-marrow, 
and  the  absence  of  siderosis  of  the  liver.     Bui  the  diagnosis  of  leukemia  doe- 


362  LEUKEMIA 

not  fit  the  facts  any  better;  for,  in  this  case,  there  was  no  absolute  increase  of 
the  white  blood-corpuscles  and  no  absolute  increase  of  the  eosinophile  cells; 
in  fact,  the  number  of  them  in  this  case  was  decidedly  diminished  (0.6  per 
cent.);  moreover.  Charcot's  crystals  were  not  present  in  the  bone-marrow. 
These  facts  scarcely  coincide  with  the  assumption  of  a  leukemia  which,  in 
this  case,  must  certainly  have  originated  in  the  bone-marrow  (it  must  be 
remembered  that  the  myelocytes  alone  constitute  one-seventh  of  all  the  leuko- 
cytes). 

We  may,  therefore,  say  that  in  this  case  we  were  dealing  with  a  severe, 
perhaps  infectious,  disturbance  of  the  process  of  formation  of  the  biood  cells 
in  the  bone-marrow,  and  that  this  affected  the  red  as  weit  as  the  white  blood- 
corpuscles,  with  the  result  that  both  remained  in  an  immature  condition,  the 
while  ceils  nut  even  leine/  perfectly  r/ranular.  This  redaction  of  the  function 
of  the  bone-marrow  in  a  few  days  led  to  the  complete  cessation  of  blood  for- 
mation, and  this  to  the  destruction  of  the  vitality  of  the  organism.  Besides 
the  cessation  of  the  function  of  the  bone-marrow,  the  function  of  the  spleen 
was  severely  damaged  as  regards  the  production  of  lymphocytes,  which 
were  produced  in  a  hurry  and  hence  entered  the  blood  chiefly  as  large 
lymphocytes. 

The  essential  feature  of  this  case  of  leukanemia  is  the  fact  that  the  devel- 
opment of  both  red  and  white  corpuscles  was  affected.  In  leukemia,  on  the 
other  hand,  it  must  be  supposed  that  the  specific  poison  is  concentrated  essen- 
tially upon  the  white  corpuscles,  sometimes  the  lymphocytes,  sometimes  the 
leukocytes,  according  to  the  nature  of  the  irritant.  The  process  in  leukemia 
is  probably  as  follows: 

By  the  continuous,  not  transitory,  action  of  the  poison,  a  more  rapid 
production  and  washing  out  of  white  cells  is  brought  about,  and  during  this 
process,  not  only  mature  forms  but  also  immature  elements,  sometimes  more, 
sometimes  less,  pass  into  the  blood — in  the  leukocytic  leukemia  the  myelo- 
cytes, in  the  lymphocytic  leukemia  large  lymphoid  cells  (which  may  lie  re- 
garded at  least  with  probability  as  immature  elements,  normally  not  yet  fit 
to  pass  into  the  blood).  The  emigration  of  the  complete  polynuclear  cells 
(and  partly  perhaps  of  the  myelocytes)  may  be  easily  explained  as  a  conse- 
quence of  their  ameboid  contractility,  whereas  the  enormous  emigration  of  the 
lymphocytes  which  in  lymphocyte  leukemia  are  incapable  of  ameboid  move- 
ment is  apparently  difficult  to  understand.  However,  I  believe  there  is  nothing 
against  the  assumption  that  the  lymphocytes,  because  of  their  production  in 
excessive  numbers,  may  also  enter  the  circulating  blood  in  large  numbers,  as 
they  do  under  normal  conditions,  i.  e.,  by  "  passive  exudation,"  owing  to  an 
unusually  strong  lymph  circulation,  etc.,  provided  the  processes  which  nor- 
mally cause  the  entrance  of  the  lymphocytes  are  more  active,  which  is  true 
to  a  varying  extent  in  different  cases. 

This  of  itself  leads  us  to  discuss  the  question  of  the  part  in  the  leukemic 
process  which  is  taken  by  the  various  organs  in  which  blood  cell  formation 
normally  takes  place.  It  may  to-day  be  regarded  as  certain  that  the  bone- 
murroir  is  particularly  implicated  in  leukemia,  not  only  in  leukocyte  leukemia 
but  also  in  lymphocyte  leukemia. 


SYMPTOMS   AND   BLOOD-CHANGES  363 

We  may  assume  that  normally  the  majority  of  the  lymphocytes  are  pro- 
duced in  the  spleen  and  lymph-glands,  and  only  a  few  in  the  bone-marrow. 
As,  however,  hyperplasias  of  the  spleen  and  lymph-glands  occur  without 
lymphemia  ("pseudo-leukemia"),  as  well  as  with  it  (lymphocyte  leukemia), 
and  since,  moreover,  there  are  cases  of  leukemia  with  lymphadenoid  changes 
of  the  bone-marrow  but  without  enlargement  of  the  spleen  or  lymph-glands, 
we  may  conclude  that  the  implication  of  the  bone-marrow,  i.  e.,  the  super- 
vention of  increased  marrow  activity  in  simple  hyperplasia  of  the  spleen  and 
lymph-glands,  represents  the  most  important  element  in  the  development  of 
leukemia  (  Neumann).  However,  in  my  opinion  this  does  not  explain  why  an 
increase  of  the  lymphocytes  in  the  blood  may  not  occur  in  hyperplasia  of  the 
spleen  and  lymph-glands  without  an  affection  of  the  bone-marrow.  As  the 
small  lymphocyte-  which  are  formed  in  tin'  lymph-glands  ander  normal  con- 
ditions permanently  enter  the  circulating  Mood,  it  is  not  apparent  why.  with 
an  increased  production  in  the  lymph-glands  and  with  a  marked  migration 
into  the  blood,  tiny  should  not  appear  there  in  greater  numbers.  On  the 
other  hand  why  do  wo  always  have  lymphemia  when  the  bone-marrow  is 
implicated?  The  explanation  that  in  hyperplasia  of  the  tissue  of  the  spleen 
and  lymph-glands  their  capsule  also  dilates,  and  therefore  (in  contrast  with 
the  conditions  in  hyperplasia  of  the  bone-marrow),  no  mechanical  migration 
of  the  lymph-cells  into  the  blood  occur-,  is  contradicted  by  the  reflection  that 
if  tin-  were  true  every  disturbance  in  the  expansile  power  of  the  capsule 
should  result  in  a  marked  overflow  of  lymph-cells  into  the  blood.  In  my 
opinion,  it  is  better  fur  the  presenl  nol  to  consider  pseudo-leukemia  at  all 
in  connection  with  leukemia,  and  also  not  to  look  for  the  nature  of  leukemia 
in  the  increase  of  the  white  Mood  cell-  alone. 

We  cannot.  I  believe,  refrain  from  asking  what  becomes  of  the  white 
blood  cells  winch  are  so  enormously  increased  in  the  organism  in  leukemia. 
That  in  health  the  leukocytes  are  partly  excreted  and  partly  destroyed  in 
the  internal  parts  of  the  body  i-  not  to  be  doubted.  If.  with  the  enormous 
increase  of  white  cell-  in  the  blood  of  leukemics,  the  consumption  does  not 
¥<>   hand    in    hand    with    the    increased    production,   a    surplus  id'   white  ceil-    in 

tin'  blood  til ii-i  result.     Bui  there  i-  no  cogenl  proof  as  yel   for  the  view  that 

there    i-   any   such    increase    in    tin-   consumption    of   leukocyte-,    which    in    this 

instance  would  have  to  he  enormous  in  order  to  keep  pace  with  the  increased 
product  ion. 

My  conception  of  the  pathogenesis  of  leukemia  i-.  therefore,  the  follow- 
ing: The  action  <>f  "  specific  agent  anises  a  pathologically  great  stimulus  tu 
tin  growth  of  the  hematopoietic  tissues  of  the  body,  which  especially  affects 

tin-  pvnit in  linn  of  White  blood-COrpUScleS.  As  n  result  of  this,  n  /limit i inj 
of   the   blood,  dl    one    lime    with    I i/m ph  m  i/l es,   ill   uimllier   lime    with    leukocytes, 

with  mature  <m<l  im  mule  re  forms  of  the  siime.  occurs.  This  change  in  the 
blood  is  continued,  partly  Inj  the  pathologic  irritation  <</'  the  blood-forming 
organs,  purl  1 1/  because  the  superfluous  white  blood  cells  are  insufficiently  used 

11 P  in  the  et onomy  of  the  body. 


364  LEUKEMIA 


DIAGNOSIS 


The  diagnosis  of  leukemia  is  in  the  majority  of  cases  not  difficult;  indeed 
it  is  very  easy  in  well  marked  cases  of  the  disease.  We  are  always  dealing 
with  leukemia  when  the  proportion  of  white  cells  to  red  is  1  to  15  or  less, 
and  the  absolute  count  of  leukocytes  or  lymphocytes  (according  to  the  case) 
is  30  to  50  times  greater  than  normal,  and  when,  besides  the  relative  and 
absolute  increase  in  the  number  of  white  cells,  an  immaturity  of  the  cells 
is  strikingly  manifest.  One  finds  in  the  blood  besides  mature  leukocytes  and 
lymphocytes  many  large  mononuclear  cells  and  abundant  myelocytes,  large 
lymphocytes  and  also  immature  forms  of  erythrocytes,  i.  e.,  nucleated  red 
blood-corpuscles  in  large  or  small  amounts,  and  in  most  striking  profusion 
in  leukocytic  leukemia.  In  leukocytic  leukemia  we  are  struck,  moreover,  by 
the  absolute  increase  of  eosinophiles  and  mast-cells. 

Having  diagnosticated  leukemia,  we  must  now  determine  to  which  form 
it  belongs,  whether  to  the  lymphocytic  or  leukocytic  type,  which  is  not  diffi- 
cult if  we  remember  the  above  mentioned  points  of  distinction. 

If  the  immature  forms  of  blood-corpuscles  are  absent  from  the  circulating 
blood,  and  if  a  "  polymorphia  "  of  the  white  corpuscles  is  lacking,  we  are  not 
dealing  with  a  case  of  leukemia,  at  least  not  of  leukocytic  leukemia,  but  with 
a  leukocytosis  in  which  myelocytes  are  never  found  (except  in  the  very  rare, 
isolated  cases  in  which  there  is  an  excessively  hasty  production  of  blood  cells). 
[Myelocytes  are  not  at  all  infrequently  found  in  leukocytosis,  i.  e.,  in  peri- 
tonitis, in  diphtheria,  in  pneumonia  and  in  malignant  diseases. — Ed.]  As 
the  blood  pictures  of  leukocytosis  and  leukemia  resemble  each  other  in  so  far 
as  an  increase  in  the  number  of  leukocytes  is  concerned,  we  must  now  discuss 
more  thoroughly  the  manner  in  which  leukocytosis  originates,  and  the  blood 
picture  of  leukocytosis. 

LEUKOCYTOSIS 

In  some  physiological  processes,  viz.,  during  digestion,  pregnancy,  after 
bodily  exercise,  etc.,  we  find,  upon  examination  of  the  blood,  an  increase  of 
the  white  cells.  [That  there  is  no  leukocytosis  of  digestion  or  of  pregnancy 
seems  to  me  demonstrated  by  the  more  careful  researches  of  recent  years. 
There  is  a  midday  leukocytosis  in  most  persons  and  this  may  coincide  with 
the  after-dinner  period.  But  after  breakfast  and  after  supper  there  are  no 
changes  to  speak  of. 

The  supposed  leukocytosis  of  pregnancy  is  not  observable,  as  a  rule,  until 
a  few  days  or  hours  before  labor;  sometimes  not  until  labor  has  begun.  After 
parturition  there  is  usually  a  well  marked  leukocytosis  lasting  several  days. 
— Ed.]  In  this  "  physiological "  leukocytosis  the  proportion  of  the  various 
forms  of  leukocytes  to  one  another  does  not  vary  greatly  from  the  normal, 
whereas  it  is  characteristic  of  pathological  leukocytosis  that,  according  to 
the  nature  of  the  disease  in  the  course  of  which  a  leukocytosis  appears,  marked 
alterations  are  noted  in  the  proportionate  numbers  of  the  various  leukocyte 
forms.    According  to  whether  the  lymphocytes  or  the  leukocytes  are  increased, 


DIAGNOSIS  365 

we  speak  of  "lymphocytosis"  or  "leukocytosis"  in  a  restricted  sense,  and 
in  this  way,  according  to  the  prominence  of  one  or  the  other  leukocyte  forms 
in  the  blood  picture,  we  may  differentiate  between  a  polynuclear  neutrophilic, 
and  an  eosinophilic,  leukocytosis. 

It  has  been  declared  at  various  times  that  the  lymphocytes  have  no  inde- 
pendent, active  motility;  if,  therefore,  in  the  course  of  pathological  condi- 
tions a  one-sided  (symptomatic)  increase  of  lymphocytes  is  noted  in  the 
blood,  we  must  consider  that  large  numbers  of  them  have  reached  the  circu- 
lating blood  by  reason  of  an  increased  cell  production  in  the  cytogenic  tissue 
of  the  lymph-glands  (and  of  the  bone-marrow  to  a  much  less  extent)  and 
by  a  more  active  lymph  circulation  ("passive  Leukocytosis,"  Ehrlich).  This 
form  of  leukocytosis,  "  lymphocytosis/3  is  quite  ran',  occurring  especially  in 
catarrhal  affections  of  the  stomach  and  intestines  of  nurslings,  in  pertussis, 
in  severe  rickets,  syphilis,  etc.,  after  injections  of  pilocarpi!)  and  tuberculin, 
and  after  extirpation  of  the  spleen. 

More  frequent  is  the  second  form  of  leukocytosis,  polynuclear  Leukocytosis. 
Various  irritations  (infectious  agents,  chemical  poison.-,  etc.)  cause  these 
leukocytes,  which  are  always  presenl  in  great  amounts  in  the  bone-marrow 
[as  well  as  in  the  capillaries  of  the  liver  and  especially  of  the  lungs. — Ed.] 
and  which,  on  account  of  their  ameboid  movement,  are  always  ready  to  pass 
into  the  blood,  to  emigrate,  and  to  enter  the  blood  by  '*  Chemotaxis  "  ("  active  " 
leukocytosis).  As  a  rule,  it  is  the  neutrophilic  polynuclear  leukocytes  which 
circulate  in  the  blood  in  large  numbers  in  leukocytosis;  i.e.,  almost  all  intoxi- 
cations and  infections  lead  to  this,  the  "usual"'  form  of  leukocytosis.  Such 
causes  are:  Poisoning  by  potassium  chlorate,  phenacetin,  oil  of  turpentine. 
albumoses,  arseniuretted  hydrogen,  etc.;  also  cachectic  conditions  as  a  result 
of  malignant  tumors,  phthisis,  severe  blood  Loss;  and.  above  all.  the  various 
infectious  diseases — pneumonia,  sepsis,  diphtheria,  erysipelas,  etc.  On  the 
other  hand,  in  certain  pathological  conditions  we  note  a  one-sided  Increase 
of  the  eosinophilic  cells  (eosinophilic  leukocytosis).  This  is  the  case  in  bron- 
chial asthma,  in  various  diseases  of  the  skin,  in  malignant  tumors,  and  espe- 
cially also  in  helminthiasis  (due  to  the  presence  of  tenia1,  ascarides,  ankylos- 
toma,  etc.,  in  the  intestine.  [As  well  as  in  echinococcus  disease,  trichiniasis, 
Bilharziosis,  trypanosomiasis  and  practically  all  the  diseases  due  to  animal 
parasites. — En.  | 

Leukemia  represents  a  morbus  sui  generis,  the  nature  of  which,  as  we  have 
seen,  depends  u pon  a  pathological  blood  formation,  i.e.,  not  only  upon  an 

excessive    increase    of    the    white    blood     cells    but     a  Lo    Upon     their    qualitative 

change  (the  passage  of  immature  forms  into  the  blood),  in  leukocytosis,  on 
the  other  hand,  the  condition  is  only  a  Functional  alteration  of  the  blood- 
forming  organs,  and  in  the  majority  of  cases  (leukocytosis  in  the  restricted 
sense)  exclusively  of  the  bone-marrow,  which  reacts  to  pathological  irritation 
by  the  formation  and  expulsion  of  large  numbers  of  normal  and  mature 
eolorless  blood-corpuscles.  This  explanation  of  Leukocytosis,  the  strict  con- 
ception of  which  as  an  increased  function  of  the  bone-marrow  was  formulated 
by   Ehrlich,  has   lately  been   fully  confirmed  experimentally   by    Rubinstein 

[and   Btill   more   fully   worked  out   by    LongCOpe   in   his  Btudies  of  the   marrow 


366  LEUKEMIA 

in  typhoid,  pneumonia,  and  peritonitis. — Ed.].  After  the  injection  of  an 
agent  causing  leukocytosis,  he  followed  step  by  step  the  changes  in  the  bone- 
marrow.  As  soon  as  the  leukocytes  appeared  in  the  blood  in  large  numbers, 
the  granular,  mature  elements  in  the  bone-marrow  almost  wholly  disappeared, 
and,  instead  of  these,  in  a  few  days,  the  immature  forms,  especially  the 
myelocytes,  increased.  The  latter,  therefore,  covered  the  loss  due  to  the 
enormous  emigration  of  the  polynuelears  into  the  blood  as  a  result  of  the 
leukocytosis.  The  spleen  and  the  lymph-glands,  however,  in  Eubinstein's 
experiments,  took  no  part  in  making  up  the  loss  of  white  corpuscles  in  poly- 
nuclear  leukocytosis,  but,  according  to  our  present  opinion  regarding  the 
separate  development  of  leukocytes  and  lymphocytes,  this  is  not  to  be  won- 
dered at. 

From  what  has  been  stated,  it  is  clear  that  the  diagnosis  of  leukocytosis  rests 
primarily  on  the  discovery  of  a  disease  which  is  recognized  as  usually  giving 
rise  to  leukocytosis.  The  diagnosis  becomes  more  certain  if  the  increase  of  the 
white  blood  cells  is  a  transitory  one  (i.  e.,  disappearing  with  the  cessation 
of  the  underlying  affection),  and  remains  from  the  onset  within  moderate 
limits.  While  in  leukemia  ratios  of  1  white  to  10  red  corpuscles,  and  even 
1  to  2,  are  quite  usual,  in  leukocytosis  there  is  a  much  slighter  relative  in- 
crease of  leukocytes,  and  only  in  exceptional  cases,  as  in  cachectic  conditions 
when  there  is  a  decided  decrease  of  the  erythrocytes  simultaneously  with 
leukocytosis,  does  it  happen  that  proportional  figures  of  1  to  20  are  observed 
for  a  long  time.  Under  such  conditions  these  cases  may  simulate  leukemia, 
but  here  the  recognition  of  morphological  alterations  in  the  white  blood- 
corpuscles  leads  to  the  correct  diagnosis,  because  the  excessive  appearance 
of  myelocytes,  eosinophiles,  and  mast-cells  in  the  circulating  blood  (in  short, 
a  markedly  polymorphous  condition  of  the  blood  elements  which  is  quite 
foreign  to  leukocytosis)  directly  favors  the  existence  of  leukemia.  The  diag- 
nosis of  the  latter  disease  is  also  aided  by  the  decided  enlargement  of  the 
spleen  and  lymph-glands,  and  the  absolute  and  relative  increase  of  uric  acid 
excretion  in  the  urine,  etc. 

These  last  named  factors  especially  must  be  taken  into  consideration  when 
we  are  dealing  with  a  lymphocytosis,  because  here  the  most  important  point 
of  distinction  between  leukemia  and  (polynuclear)  leukocytosis,  the  poly- 
morphia  of  the  blood  cells,  is  of  no  avail.  In  practice,  however,  the  diagnosis 
of  lymphocytosis  is  never  doubtful,  the  difficulty  in  differentiating  between  a 
lymphocytosis  and  a  feebly  developed  lymphocytic  leukemia  being  theoretic 
rather  than  actual.  [On  the  contrary,  mistakes  have  actually  occurred.  See 
Steven  (Lancet,  1902,  vol.  xx)  and  Cabot  ("  Clinical  Examination  of  the 
Blood,"  5th  edition,  1904,  p.  194). — Ed.].  For,  in  the  acute  form  of  lympho- 
cytic leukemia,  the  large  lymphocytes  almost  always  predominate,  and  this 
alone  is  sufficient  to  prevent  confusion  between  lymphocytic  leukemia  and 
lymphocytosis;  even  in  chronic  lymphocytic  leukemia  the  large  lymphocytes 
are  not  entirely  absent  in  the  microscopical  preparations,  although,  in  the 
great  majority  of  cases,  only  small  leukocytes  are  found. 

Above  all,  the  usually  enormous  increase  of  lymphocytes  in  lymphocytic 
leukemia,  the  progressive,  pernicious  nature  of  the  disease  compared  with  the 


TREATMENT  367 

transitory,  benign  character  of  the  increased  number  of  lymphocytes  in 
lymphocytosis,  determines  the  correcl  diagnosis.  On  the  other  hand,  the 
following  symptoms  poinl  to  leukocytosis :  The  absence  of  enlargement  of 
the  spleen  and  of  the  lymph-glands  which  is  almost  always  presenl  in  lympho- 
cytic leukemia;  and.  secondly,  the  presence  of  a  primary  disease  which  would 
lead  to  leukocytosis  (gastro-entcritis  infantum,  etc.). 


PROGNOSIS 

The  prognosis  of  leukemia  may  he  briefly  summed  up:  (7  is  absolutely 
unfavorable;  death  is  fh<-  only  outcome  of  the  disease.  This  is  true  no!  only 
of  the  acute  form  of  leukemia  in  which  death  occurs  usually  in  a  (>'\v  dav- 
or weeks,  hut  also  of  chronic  leukemia,  of  leukocytic  leukemia,  as  well  a-  of 
chronic  lymphocytic  leukemia.  Eowever,  in  both  forms  of  chronic  leukemia, 
especially  leukocytic  leukemia,  remissions  may  occur  with  considerable  im- 
provement of  symptoms,  and  the  disease  may  sometimes  las!  for  from  one 
to  four  years.  But  since  we  have  learned  positively  to  recognize  leukemia 
by  new  methods  of  blood  examination,  tu,  actual  cure  has  as  yet  been  ob- 
served. From  this  standpoint  we  must  look  with  suspicion  on  "recoveries" 
reported  from  time  to  time,  and  I  do  not  hesitate  to  pronounce  as  doubtful 
a  case  of  cure  which  came  under  my  observation  twenty-five  years  ago,  since 
the  diagnosis  made  at  that  time  does  not  conform  to  the  requirements 
to-day. 

This  gloomy  view  concernins:  the  prognosis  of  leukemia  is.  however,  based 
on  the  present  state  of  our  experience,  and  it  is  to  be  hoped  thai  when  we  obtain 
more  e\aet  knowledge  of  the  nature  of  the  specific  poison  causing  this  disease, 
our  therapy  will  hecome  more  effectual,  and  the  prospects  of  cure  more 
favorable. 

TREATMENT 

At  the  present  time  there  is  nothing  that  can  he  regarded  a-  the  fulfilment 
of  an  indicatio  morbi.     All  that  ha-  Keen  thus  far  attempted   in  treatmenl 

may  he  regarded  merely  as  efforts  to  feel  our  way.  and  these  have  so  far  I □ 

abandoned  as  soon  as  undertaken.  A  few  drugs  only  have  held  their  place 
in  the  treatment  of  leukemia,  and  by  mosi  physicians,  a-  well  as  by  myself, 
are  employed  faute  de  mieux,  though  it  i-  true  that  the  long  duration  of  a 
U'\v  cases  treated  in  this  manner,  ami  the  transitory  hut  decided  remissions 
in   the  course  of  the  disease   may,  at    leasl    in    pail,   he   referred    to  the  action 

of  tin'  remedy. 

Arsenic  is  the  drug  which  mosi  deserves  our  confidence.  During  it-  ad- 
ministration, we  see  in  some  cases  an  improvemenl  in  the  condition  of  the 
blood  (not  only  an  increase  in  the  number  of  red  hut  also  a  decrease  in 
the  number  of  the  white  corpuscles ).  an  arresl  of  the  -picnic  enlargement,  and 
the  disappearance  of  the  hemorrhagic  diathesis. 

The  besl  way  of  administering  arsenic  i-  in  the  form  of  Fowler's  solution 

with   two  part-  of  aqua  ci una inonii  : 


368  LEUKEMIA 

I£   Solutio  kalii  arsenicosi 10.0 

Aq.  cinnamomi   20.0 

M.,  D.,  S. :  Gtt.  xv-xxx,  three  times  daily. 

We  begin  with  15  gtt.  t.i.d.  (taken  after  meals),  and  increase  gradually, 
i.  e.,  after  one  week  20  gtt.  t.i.d.,  after  the  second  week  25  gtt.  t.i.d.,  and  after 
the  third  week  30  gtt.  t.i.d. ;  this  dose  we  maintain  for  some  time.  I  am  not 
enthusiastic  regarding  the  subcutaneous  use  of  arsenic.  The  injection  of 
arsenic  into  the  circulating  blood  could  only  be  desirable  if  the  results  obtained 
by  this  method  were  incomparably  more  brilliant  than  after  the  administration 
of  arsenic  by  the  mouth,  and  this  is  decidedly  not  the  case. 

Another  remedy  producing  apparently  favorable  results  is  quinin.  Its 
action  is  asserted  to  be  remarkable,  especially  if  it  be  combined  with  arsenic 
or  iron.  In  this  respect,  the  mineral  waters  containing  arsenic  and  iron,  as 
Levico  and  Roncegno  water,  and  the  Levico  water  used  in  the  form  of  baths, 
deserve  consideration. 

In  the  majority  of  cases  the  erythrocytes  decrease  to  one-half  their  number 
or  less  with  the  increase  of  white  corpuscles  (at  least  in  the  latter  course  of  both 
leukocytic  and  lymphocytic  leukemia),  and  here  the  administration  of  arsenic, 
iron  and  quinin,  whose  favorable  influence  on  the  red  corpuscles  cannot  be 
denied,  is  warranted  from  a  theoretical  standpoint,  as  well  as  empirically. 

Iodin  preparations,  formerly  prescribed  to  some  extent,  have  recently  been 
less  used ;  no  appreciable  results  of  their  use  have  been  noticed.  The  same 
is  true  of  phosphorus  in  doses  of  0.001  to  0.005,  which  has  been  praised,  espe- 
cially by  English  physicians. 

Two  therapeutical  measures  which  were  recently  hailed  with  enthusiasm, 
oxygen  inhalations  and  organotherapy  (preparations  made  from  lymph-glands 
and  bone-marrow),  have  produced  no  striking  results,  although  amelioration 
and  a  slower  progress  of  the  disease  have  been  supposed  to  follow  their  admin- 
istration. In  general,  what  has  been  said  of  the  administration  of  arsenic, 
iron,  and  quinin  is  true  also  of  this  method  of  treatment.  We  may  use  these 
remedies,  indeed,  we  must  use  them,  but  we  can  only  hope  for  a  partial  suc- 
cess; the  disease  up  to  this  time  has  been  invariably  fatal,  but,  as  a  rule, 
lasts  a  year  or  longer,  and  calls  for  a  display  of  humanity  on  the  part  of  the 
physician  which  is  not  shown  by  quietly  folding  his  hands  and  rejecting  any 
method  of  treatment  which  offers  the  patient  the  slightest  hope  of  recovery  or 
even  improvement. 

Although  I  strongly  recommend  the  trial  of  the  above-mentioned  thera- 
peutic measures  in  the  treatment  of  leukemia,  just  as  strongly  must  I  con- 
demn local  procedures.  Not  only  does  the  lack  of  results  militate  against  their 
use,  but  we  are  thoroughly  convinced  that  the  nature  of  leukemia  is  not  to 
be  found  in  the  affection  of  the  spleen  or  of  any  individual  lymph-gland,  nor 
in  any  other  organ  accessible  to  local  treatment.  I  believe  that  the  time  has 
come  to  discontinue  all  efforts  to  cure  the  disease  by  injections  of  arsenic, 
ergotin,  etc.,  into  the  spleen,  by  faradization  or  galvanopuncture  of  the  organ, 
or  even  by  extirpation  of  the  glands,  or  by  splenectomy  which,  without  an 
exception,  has  been  rapidly  followed  by  death. 


TREATMENT  369 

It  is  much  more  sensible  to  retard  the  increased  albumin  waste  in  the 
organism  by  rational  diet,  or,  in  its  later  stages,  to  compensate  it,  at  least 
partially,  by  increased  nutrition.  A  nourishing  diet,  rich  in  nitrogen,  is 
therefore  to  be  advised  because  a  well-nourished  organism  will  always  offer 
more  resistance  to  the  disease  than  one  debilitated  by  cachexia.  To  strengthen 
the  body,  besides  judicious  diet,  moderate  systematic  exercise  in  the  open  air 
and  the  avoidance  of  too  great  physical  exertion  nni-t  be  insisted  upon. 

Of  course,  the  ind  initio  symptomatica  may  require  different  expedients. 
Marked  diarrhea  must  be  combated  by  tannigen  and  opium,  dyspeptic  symp- 
toms by  regulation  of  the  diet,  lavage,  etc..  exhausting  sweats  by  camphoric 
acid  and  atropin.  a  marked  hemorrhagic  diathesis  by  ergotin  or  other  prepara- 
tions of  ergot  in  large  doses  (ergotin  0.2.  five  times  daily,  secale  10.0  to  150, 
to  be  used  in  two  days),  cardiac  asthenia  by  camphor,  etc.  It  is  unnecessary 
to  enumerate  these  indications  in  greater  detail,  for  the  treatment  of  individ- 
ual symptoms  and  complications  is  in  accordance  with  the  same  rule-  as  in 
other  diseases.  Only  T  must  caution  against  the  too  liberal  use  of  drugs  in 
leukemia:  we  must  not  forgel  iliat  we  are  dealing  with  the  debilitated,  the 
desperately  ill.  in  whom  it  might  be  dangerous  to  act  according  to  the  prin- 
ciple "' anceps  remedium  melius  quam  nullum." 

[The  treatment  of  leukemia  by  X-rays  certainly  deserves  mention.  Since 
Senn's  original  observation  in  1902,  30  or  lo  cases  have  been  published  in  this 
country  in  which  the  disease  has  been  treated  by  exposure  of  the  spleen  or 
(in  lymphatic  cases)  of  the  spleen  and  gland-  to  the  Eoentgen  rays. 

Cases  are  treated  daily,  biweekly,  or  weekly  according  to  the  condition  of 
the  skin  and  its  ability  to  resist  "  burns."  In  a  few  cases,  the  rays  have  been 
made  to  fall  upon  the  long  bones. 

In  the  majority  of  these  cases  improvement,  sometimes  remarkable  and 

(bo  tar)  lasting,  has  followed  the  treatment.     A  few  cases  have  I n  altogether 

unaffected,  a  number  have  relapsed  after  temporary  improvement,  and  a  small 
number  have  been  worse  after  the  treatment.     In  acute  febrile  cases  there  has 

been    no   SUCCe8S. 

The  rationale  of  the  t  real  incut  is  not  at  all  clear,  for  the  exposures  have 
usually  been  made  over  the  spleen,  and  not  over  the  marrow  when>  the  disease 
is  mo«1  active.  We  know  from  the  researches  of  Warthin  and  others  that 
the  X-rays  have  a  specific  leukocytolytic  effed  on  the  blood  forming  organs 
of  animals,  and  if  the  over-productiou  of  leukocytes  were  occurring  in  the 
leukemic  spleen  instead  of  in  the  marrow  the  effeel  of  the  X-ray  would  be 
comprehensible.  At  present  it  remains  a  mystery,  but  it  i-  none  the  less 
advisable  that  all  subacute  and  chronic  cases  of  either  variety  of  leukemia 
should  be  given  X-ray  treatment,  which  at  presenl  oiler-  the  besl  possibility 
of  retarding  (or  curing?)  the  disease.     Ed.] 


26 


PSEUDO-LEUKEMIA 
(HODGKIN'S   DISEASE  AND   BANTI'S   DISEASE) 

By  H.    SENATOR,  Berlin 

We  often  meet  with  cases  characterized  by  the  following  lesions:  a  more 
or  less  well-developed  anemia,  together  with  multiple  lymph-gland  enlarge- 
ments, a  very  decided  enlargement  of  the  spleen,  or  both.  This  glandular  and 
splenic  enlargement  also  occurs  in  leukemia,  which,  however,  differs  from 
pseudo-leukemia  in  possessing  a  characteristic  condition  of  the  blood,  particu- 
larly a  great  increase  of  leukocytes,  which  is  not  present  in  pseudo-leukemia. 

To  this  difference  from  leukemia,  which  these  cases  often  resemble  greatly, 
Bonfils  and  Wilks  in  the  year  1856  were  the  first  to  call  attention,  though 
Virchow  had  described  leukemia  eleven  years  previously,  in  IS  1.3. 

Soon  the  publication  of  cases  of  this  kind  increased,  and  new  names  were 
repeatedly  invented  for  them.  Bonfils  designated  his  cases  as  "  cachexia  with- 
out leukemia";  Wilks  called  his  "anemia  lymphatica,"  and  later  "  Hodg- 
k in's  disease,"  since  Hodgkin  had  described  such  cases  explicitly,  long  before 
the  discovery  of  leukemia,  that  is,  in  the  year  1832.  The  counterpart  to 
"anemia  lymphatica  "  (in  which  enlargement  of  the  lymph-glands  is  the  only 
lesion  or  is  much  more  marked  than  that  of  the  spleen)  is  the  term  "  anemia 
splenica,"  a  condition  in  which  the  lesions  are  confined  to  the  spleen.  The 
combination  of  both  conditions  has  been  called  "anemia  Ivmphatico-lienalis." 
Still  other  names  have  been  proposed  which  I  do  not  intend  to  mention,  since 
they  are  based  wholly  on  the  anatomical  condition  without  regard  to  the 
clinical  phenomena,  and  are  not  adapted  to  all  the  cases  belonging  in  this 
category.  They  have  all  been  superseded  by  the  term  introduced  by  J.  Cohn- 
heim  in  the  year  1865,  "  pseudo-leiikemia,"  which,  in  spite  of  all  objections, 
has  maintained  its  place  until  to-day  and  will  probably  maintain  its  vogue 
for  a  long  time. 

It  is  true  that  "  pseudo-leukemia "  has  become  a  collective  name  for  a 
number  of  different  affections,  but  since  these  affections  cannot  always  be 
separated  from  one  another,  and  since  this  name  is  short  and  conveniently 
expresses  what  is  common  to  them  all  (namely,  that  they  resemble  leukemia 
but  still  are  not  leukemia,  at  least  clinically),  the  name  pseudo-leukemia  will 
be  employed  in  this  article. 

The  difficulties  in  the  nomenclature  of  this  disease  are  the  same  as,  for 
example,  in  "ileus."  Every  physician  knows  that  the  clinical  picture  desig- 
nated by  Uiis  name  is  brougltt  about  by  various  anatomical  changes  of  the 
370 


HODGKIX'S   DISEASE  371 

intestine.  But  as  we  arc  not  always  able  to  differentiate  these  changes  we 
cannot  discard  the  name  which  describes  the  typical  clinical  picture. 

This,  of  course,  mu-t  not  prevent  us  from  investigating  so  far  as  is  possi- 
ble the  anatomical  conditions  in  each  individual  case  of  pseudo-leukemia,  and 
finding,  if  we  can.  the  exad  lesion  present,  particularly  as  support  may  be 
gained  in  this  way  for  prognosis  and  therapy.  [The  studies  of  Dorothy  Reed, 
confirmed  by  those  of  Longcope  and  of  Simmon-,  have,  I  think,  established 
Hodgkin's  disease  upon  a  definite  histological  basis,  and  differentiated  it  alike 
from  tuberculosis,  from  sarcoma,  and  from  leukemic  infiltrations.  In  view  of 
these  findings,  the  diagnosis  can  and  should  he  made  by  the  excision  of  one  (or 
more  [f  need  be)  of  the  superficial  lymph-glands  and  examining  it  histo- 
logically.— Ed.] 

The  organs  which  are  to  he  considered  in  pseudo-leukemia,  the  lymph- 
glands  and  the  spleen,  are  almosl  always  simultaneously  affected,  although  not 
often  to  the  same  extent.  In  pseudo-leukemia  we  know  but  little  regarding 
the  third  organ  which  is  important,  or  probably  important,  in  blood  forma- 
tion, namely,  the  bone-marrow ;  it  has  sometime-  been  found  hyperemic  and 
of  the  same  consistence  as  in  leukemia,  but  in  regard  to  this  further  investiga- 
tion is  necessary. 

In  the  majority  of  cases  the  enlargement  of  the  lymph-glands  is  more  con- 
spicuous  than  thai  of  the  spleen.  I [ence  some  clinicians  recognize  as  --  pseudo- 
leukemia '"  only  those  multiple  lymph-gland  enlargements  firsl  described  by 
Hodgkin,  and  distinguish  sharply  the  cases  in  which  enlargement  of  the  spleen 
is  more  prominent,  or  is  preseni  alone.  To  me  it  appears  that  this  limita- 
tion of  the  conception  " pseudo-leukemia "  is  unwise,  for  an  enlargemenl  of 
the  lymph-glands  alone  or  of  the  spleen  alone  rarely  occurs.  Even  though 
during  life  we  find  many  cases  with  decided  enlargemenl  of  the  glands,  and 
no  apparent  enlargemenl  of  the  spleen,  still  I  believe  that  at  the  autopsy  the 
spleen  is  almosl  invariably  found  enlarged.     On  the  other  hand,  in  cases  with 

predominant  enlargemenl  of  the  spleen,  s< i  enlarged  lymph-glands  are  almosl 

always  found  at  the  autopsy,  if  not  the  superficial  ones  then  those  of  the  abdo- 
men or  of  the  thoracic  cavity.  A  sharp  distinction  therefore  cannot  be  drawn 
here,  and  there  are  huhu/  cases  in  which  the  spleen  and  lymph-glands  are 
equally — or,  rather,  proportionately  enlarged. 

If,  however,  vre  wi-h  to  lay  special  stress  either  upon  lymph-gland  enlarge- 
menl or  upon  the  spleen,  in  the  former  case  we  may  use  the  terms  "pseudo- 
leukemia lymphatica"  or  true  Hodgkin's  disease,  in  the  latter  case  "pseudo- 
leukemia lienalis"  or  "splenica";  finally  the  cases  with  equal  implication  of 
the  lymph-glands  and  of  the  spleen  may  he  designated  a-  "pseudo-leukemia 
lymphatico-lienalis  "  or  "  spleno-lymphatica." 

We  -hall  lir-t  describe  the  more  common  form,  pseudo-leukemia  lymphatica 

or  I  hui  ill,  hi's  i/is,  a 

HODGKIN'S    DISEASE 

The  mo-t  conspicuous  and  usually  the  tir-t  symptom  i-  the  enlargement  "f 
a  gland  nr  of  a  fin-  glands  in  ihr  neck,  oftenesi  at  the  angle  of  the  jaw.  This 
enlargemenl  occurs  a-  a  rule  quite  gradually,  bo  that  only  in  the  coura 


372  PSEUDO-LEUKEMIA 

several  weeks  or  even  months  does  it  become  noticeable.  By  this  time  the 
individual  gland  has  attained  the  size  of  a  cherry  or  a  small  walnut,  or  a 
group  of  swollen  glands  has  -become  conspicuous  to  sight  and  touch. 

The  swellings  are  painless.  After  a  latent  period  of  varying  duration 
they  begin  to  increase  following  a  definite  course  next  to  be  described.  First, 
more  glands  are  involved,  usually  those  in  the  neighborhood  of  the  one  first 
affected,  i.  e.,  those  in  the  lower  part  of  the  neck  or  in  the  back  of  the  neck, 
later  those  in  the  axilla,  at  the  elbow,  in  the  inguinal  region,  occasionally  those 
in  the  popliteal  space.  Next  comes  an  increase  in  the  size  of  the  individual 
glands,  which  may  become  as  large  as  a  man's  fist  or  even  larger.  The  glands 
of  the  neck  and  axilla,  which  are  those  first  affected,  are  always  most  advanced 
in  growth,  while  those  of  the  inguinal  region  and  of  the  thigh  are  less  mark- 
edly enlarged. 

The  enlarged  glands  can  usually  be  felt  and  defined  with  ease;  in  other 
cases  they  are  more  or  less  matted  together;  they  are  more  frequently  soft 
than  hard  in  consistence,  and  in  many  cases  they  may  be  readily  moved  about. 
As  a  rule  the  skin  above  the  glands  can  easily  be  raised,  but  shows  no  other 
change.  The  spleen,  ß,§  has  been  said,  in  this  form  of  pseudo-leukemia,  Hodg- 
kin's  disease,  is  almost  always  implicated,  but  to  a  much  less  degree  than  the 
glands,  so  that  its  enlargement  cannot  always  be  determined  with  certainty 
during  the  life  of  the  patient. 

Add  to  these  facts  the  vista  of  a  gradual  increase  in  the  glandular  enlarge- 
ment, while  almost  exactly  in  proportion  to  this  the  general  condition  of  the 
patient  deteriorates  so  that  he  oecomes  anemic,  loses  his  strength  and  emaciates, 
and  we  are  in  possession  of  the  most  important  features  of  the  clinical  picture. 

But  in  these  outlines  the  entire  symptom-complex  is  by  no  means  revealed. 
Indeed  it  may  be  very  complicated. 

The  symptoms  are  in  part  purely  local  consequences  of  the  existence  of 
the  tumors,  and  hence  depend  particularly  upon  the  pressure  which  these 
glands  exert,  or  upon  the  metastases  which  they  produce.  But  there  are  other 
symptoms  of  a  general  nature,  which  result  partly  from  the  anemia  and 
cachexia,  partly  from  the  actual  nature  of  the  disease  which  is  wholly  unknown 
to  us. 

Before  recounting  the  symptoms  I  must  add  that,  besides  the  glandular 
enlargements  which  are  externally  visible  and  palpable,  there  is  almost  in- 
variably an  enlargement  of  the  internal  lymph-glands,  those  of  the  thoracic 
and  abdominal  cavities.  These  internal  glands  are  sometimes  large,  some- 
times small  and  therefore  not  always  clinically  recognizable.  Cases  do  occur 
in  which  only  the  internal  lymph-glands  are  enlarged,  the  external  ones  not 
at  all  or  to  an  exceedingly  slight  degree.  I  have  myself  seen  a  very  remark- 
able case  of  this  type,  to  which  I  shall  recur  later.  We  must  admit  that  such 
cases  are  not  likely  to  be  diagnosticated  clinically ;  the  pathologist  designates 
them  as  multiple  lymphomata  or  as  lymphomatosis,  the  same  title  given  by  him 
to  the  external  enlargements  which  occur  in  Hodgkin's  disease. 

It  is  these  internal  glandular  enlargements  which  bring  about  the  most 
severe  pressure  phenomena,  especially  in  the  thorax  where  there  is  less  room 
for  growth  than  in  the  abdominal  cavity.     Enlarged  glands  in  the  anterior 


HODGKIX'S   DISEASE 


373 


mediastinal  space  press  particularly  upon  the  innominate  vein,  and  thus  pro- 
duce swelling  of  the  veins  of  the  neck  and  thr  wall  of  the  chest  with  cyanosis 
and  edema  of  the  face,  to  which  may  be  added  dropsical  effusions  into  one  or 
both  pleurae.  These  phenomena,  however,  are  not  so  frequent  or  so  marked 
as  with  other  tumors  and  tumor-like  formations  in  the  thoracic  cavity,  for  the 
glandular  swellings  are  usually  softer  and  less  resistant  than  other  tumors.  It 
is  true  that  harder  forms  occasionally  occur  depending  upon  histological  vari- 
ations the  discussion  of  which  will  follow  later  on,  and  these  hard  tumors  may 
produce  all  the  phenomena  of  pressure  and  stasis. 

The  development  of  dropsical  effusions  may  be  produced  in  three  ways: 
(1)  by  venous  stasis;  (2)  by  displacement  of  the  lymphatic  trunks,  caus- 
ing a  hindrance  to  the  absorp- 
tion of  tissue  fluid;  and  (3) 
by  progressive  anemia  and  ca- 
chexia. 

More  common  than  stasis 
phenomena  are  difficulties  in 
respiration.  These  are  caused, 
(1)  by  direct  pressure  which 
the  glandular  swellings  exert 
upon  the  larynx,  trachea  or 
bronchi;  (2)  by  pressure  upon 
the  vagus,  or  (very  frequently) 
ii  I  mil  the  recurrent  laryngeal 
nerve;  (3)  by  the  decrease  of 
erythrocytes  which  arc  the  d 
sarv  oxygen  carriers  in  the  func- 
tion of  respiration.  Difficulty 
in  deglutition  as  the  result  of 
pressure  upon  the  pharynx  or 
esophagus  is  rare. 

Enlargements  of  the  thoracic 
lymph-glands  also  produce  both 
dropsical  effusions  into  the 
pleura,  and  true  inflammations 
of  the  pleura  (unilateral  or 
bilateral),  which  cannot  always 
be  differentiated  from  dropsy, 
Bince  there  are  fluids  intermedi- 
ate between  dropsical  effusions 
(transudates)  and  Inflamma- 
tory effusions   (exudates). 

Another  Bymptom  which  is  probably  to  be  referred  to  the  local  pressure 
exerted  by  the  glandular  tumors  is  neuralgia.  I  have  seen  it  mos!  frequently 
in  the  lower  extremities,  especially  in  the  course  of  the  Bciatic  nerve  or  the 
crural  nerve.  In  a  case  of  this  kind  in  which  the  patient  was  troubled  with 
painful  contractions  in  the  lefi  ilio-psoaa  muscle,  I  could  feel  in  the  corre- 


1  :..  21. — Case  OF  Hoik. kin'-  Dial  LSI  W  Db,  >\i- 
qtobr's  Ward  in  the  Jbffebsom  Medical 
Collbqb  Bospitax*  <  *i  lerated  upoD  by  Prof.  W. 
W.  Keen  for  the  removal  of  large  muses  of  lymph- 
!_■  1 ; 1 1 1 . 1  -  pressing  upon  the  trachea,  which  produced 
:ii tacks  <if  Buffocat ion. 


374  PSEUDO-LEUKEMIA 

sponding  abdominal  region  distinct  glandular  enlargements  which  probably 
exerted  pressure  upon  the  muscle  and  the  nerve  which  supplied  it,  and  thus 
caused  the  pains  and  contractions. 

The  urine  shows  nothing  special;  its  composition  is  that  which  is  usual  in 
anemia  provided  no  complications  are  present.  Occasionally,  as  in  leukemia, 
it  is  found  conspicuously  rich  in  alloxur  bodies,  particularly  uric  acid.  These 
bodies,  together  with  the  nucleo-histon  which  was  once  found  in  the  urine  in 
pseudo-leukemia  by  A.  Jolles,  are  explained  by  an  increased  destruction  of 
leukocytes.1 

Finally,  as  a  frequent  but  not  invariable  symptom,  we  must  mention  hem- 
orrhages from  various  organs,  particularly  from  the  nose  and  in  the  skin  in 
the  form  of  petechia1  of  varying  size,  rarely  as  larger  effusions  of  blood.  It 
appears  to  me  that  the  tendency  to  hemorrhage  is  particularly  great  in  cases 
with  glandular  enlargements  in  the  internal  parts  of  the  body,  in  the  thorax, 
and,  above  all,  in  the  abdominal  cavity.  The  case  previously  referred  to,  in 
which  only  these  internal  glands  were  enlarged  (and  very  decidedly  so),  ran 
its  course  with  the  clinical  picture  of  Werlhofs  dispose,  i.  e.,  with  hemorrhages 
from  the  nose  and  mouth,  hematemesis,  and  blood  in  the  urine,  but  without 
other  noteworthy  symptoms  except  slight  fever.  The  autopsy  showed  hemor- 
rhages in  almost  every  organ,  and  numerous  lymphomata  in  the  thorax  and 
abdominal  cavity  of  which  we  had  no  suspicion  during  the  patient's  life. 

Shall  we  look  upon  these  glands  äs  the  cause  of  the  hemorrhages?  This 
is  hardly  possible,  for  they  are  invariably  absent  in  Werlhofs  disease,  while, 
on  the  other  hand,  glandular  enlargement  is  often  present  without  any  tend- 
ency to  extensive  hemorrhages.  We  can  only  say  that  glandular  enlarge- 
ments sometimes  lead  to  a  radical  change  in  the  blood  in  consequence  of  which 
hemorrhages  occur,  and  that  these  changes  are  particularly  noted  when  the 
lymph-glands  of  the  internal  parts  of  the  body  are  diseased. 

In  this  case,  as  I  have  said,  only  the  internal  lymph-glands  were  enlarged  : 
in  other  cases  the  lymph-gland  chains  situated  in  the  digestive  canal,  i.e.,  the 
tonsils,  the  glands  of  the  mucous  membranes  of  the  mouth  and  cheek,  the 
solitary  and  agminate  glands  of  the  intestine  may  be  affected,  with  or  without 
involvement  of  the  external  lymph-glands.  In  consequence  of  these  enlarge- 
ments all  sorts  of  otherwise  inexplicable  disturbances  occur. 

Fever  does  not  belong  to  the  typical  picture  of  Hodgkin's  disease.  Xow 
and  then  slight  rises  in  temperature  occur,  particularly  when  fresh  glandular 
enlargements  develop  rapidly,  hut  fever  is  not  characteristic,  and  in  some 
cases  may  be  entirely  absent  until  the  anemia  becomes  very  grave,  or  until 
near  the  end  of  life.  This  last  type  of  fever  corresponds  to  the  febrile  condi- 
tions which  are  observed  in  other  severe  anemias.  Of  course  there  may  be  at 
any  period  in  the  disease  a  pyrexia  due  to  complications. 

I  am  not  unmindful  of  the  fact  that  some  isolated  cases  have  been  described 
in  which  fever  was  a  most  prominent  symptom,  but  which,  nevertheless,  have 
shown  in  the  main   the  clinical  course  of  Hodgkin's  disease.      In   these  cases 

i  From  the  communication  of  Jolles  it  could  not  be  determined  whether  in  his  case 
a  lymphatic  or  a  lienal  pseudoleukemia  was  present. 


HODGKLVS   DISEASE  375 

the  fever  is  usually  remittent  or  intermittent,  with  regular  or  irregular  pauses 
some  of  which  last  several  days  (recurring).  Such  cases  have  been  described 
by  Pell,  Ebstein  and  others  as  "chronic  relapsing  fever"  or  as  "recurring 
glandular  fever."  But  in  many,  perhaps  in  the  majority,  of  tin-''  cases,  tuber- 
cle bacilli  and  other  changes  indicating  tuberculosis  have  been  found  in  the 
glands,  and  the  question  has  therefore  arisen  and  been  discussed  whether  these 
cases  should  be  designated  as  "  pseudo-leukemia." 

DIAGNOSIS 

This  brings  us  to  the  difficult  realm  of  diagnosis,  difficult  for  the  reason 
mentioned  at  tin:  beginning  of  the  article,  viz.,  because  the  conception  of 
••  pseudo-leukemia  "  is  not  a  sharply  defined  one,  or,  more  accurately  expressed, 
because  there  is  no  unanimity  as  to  which  glandular  enlargements  are  to  be 
considered  as  belonging  to  the  disease.  There  is  general  agreement  only  on 
one  point,  that  all  case-  of  secondary  or  symptomatic  adenitis,  i.e..  all  those 
which  appear  in  the  course  of  other  infections  and  are  in  causal  relation  with 
them,  are  not  to  be  designated  as  "  pseudo-leukemia,"  but  only  those  appearing 
as  primary,  multiple,  glandular  enlargements  which  dominate  the  clinical 
picture. 

Such  lymph-gland  enlargements,  however,  are  by  no  means  always  of  one 
type;  indeed,  from  a  pathological  standpoint  they  vary  greatly.  I  have  already 
mentioned  that  in  the  cases  described  a-  "chronic  relapsing  fever,"  or  as 
"recurring  glandular  fever,"  tuberculosis  is  often  found  in  the  enlarged 
lymph-glands.  But  it  is  also  true  that  in  a  Large  number  of  the  cases  described 
as  '"  pseudo-leukemia  "  and  showing  the  typical  clinical  picture  of  that  disease 
without  fever  or  with  only  an  occasional  rise  in  temperature,  tuberculosis  of 
(lie  glands  has  been  found.  In  other  cases  anatomical  investigation  ha-  re- 
vealed sarcomatous  changes,  ami  the  disease  for  this  reason  ha-  Keen  desig- 
nated  lympho-sarcomatosis  (Kundrat).  Finally,  in  still  other  cases  the 
glandular  swellings  resembled  leukemic  lymphomata. 

This  latter  form  of  multiple  lymph-gland  enlargement,  and  this  alone, 
Ehrlich  and  Pinkus  desire  to  have  designated  a-  "  pseudo-leukemia."  They  de- 
fine the  latter  as  a  disease  with  lymphadenoid  cell-accumulations  which  in  every 
respecl  resemble  the  lymphatic  leukemic  form,  running  its  course  with  an  in- 
crease of  the  lymphocytes  at  the  expense  of  the  multinuclear  leukocytes  but 
without  any  material  increase  in  the  total  number  of  the  leukocytes.  Their  pro- 
portion to  the  erythrocytes  is  -aid  not  to  exceed  l  to  200  or  1  to  100.  In  such 
cases  the  lymphadenoid  proliferations  occur,  not  only  in  the  lymph-glands,  but 
in  the  organs  of  lh<<  chest  and  abdominal  cavity  and  /'//  ///<•  shin,  ju-t  a-  in  lym- 
phatic leukemia.  Whether  the  bones  are  affected  in  pseudo-leukemia  as  in 
leukemia  i-.  a-  I  have  already  remarked,  -till  questionable. 

This  discovery  represent-  (if  true)  an  essential  advance  in  the  conception 
of  pseudo-leukemia,  even  although  for  the  time  it  ha-  no  greal  practical  impor- 
tance, particularly  for  clinical  diagnosis.  For,  in  the  iir-t  place,  if  the  blood 
condition  required  by  Ehrlich  and  Pinkus  is  actually  present,  the  differentia- 
tion of  pseudo-leukemia  from  leukemia  may  he  difficnll  or  even  impossible^ 


376  PSEUDO-LEUKEMIA 

The  ratio  of  white  cells  to  red  cells  which  is  set  up  as  a  limit  (namely,  1  to 
200  or  1  to  100)  allows  wide  space  for  variations  in  individual  opinions; 
indeed,  such  a  ratio  is  often  found  in  well-recognized  cases  of  leukemia. 

Further,  it  is  not  easy  to  determine  during  life  that  the  glandular  enlarge- 
ment actually  depends  upon  lymphadenoid  proliferation.  Even  if  an  en- 
larged gland  is  extirpated,  and  these  proliferations  are  found  in  it,  we  cannot 
conclude  with  certainty  from  this  that  in  all  the  other  enlarged  glands  the 
same  changes,  and  only  these,  are  present,  and  that  the  condition  is  not  due 
in  part  to  other  processes,  particularly  tuberculosis,  a  combination  which  has 
been  actually  observed  (Askanazy,  Fischer,  Freudweiler  and  others).  Fur- 
ther, the  blood  conditions  designated  as  characteristic  by  Ehrlich  and  Pinkus, 
an  increase  of  lymphocytes  without  much  if  any  increase  of  the  leukocytes  is 
not  constant,  a  fact  of  which  I  have  convinced  myself  in  at  least  one  case  after 
prolonged  observation.  The  proportion  of  the  mononuclear  to  the  polynuclear 
leukocytes  varies,  and  for  a  time  may  be  even  normal.  The  increase  in  lympho- 
cytes is  not  always  present  from  the  onset.  Finally,  I  do  not  believe  that  we 
can  exclude  the  possibility  of  finding  the  blood-picture  required  by  Ehrlich 
and  Pinkus,  in  connection  with  glandular  enlargements  which  do  not  show 
the  pure  leukemic  character,  i.  e.,  with  tuberculosis  or  Sarcomatosis  of  the 
glands,  and  especially  with  the  complicated  or  mixed  forms  previously  men- 
tioned. [The  Ehrlich-Pinkus  formula  certainly  is  not  present  in  every  case 
of  pseudo-leukemia — and  is  not  at  all  uncommon  in  other  diseases — e.  g.,  in 
debilitated  and  neurasthenic  conditions,  in  variola,  in  some  syphilitic  cases, 
and  in  some  acute  septic  enlargements  of  the  lymph-glands. — Ed.] 

The  greatest  difficulty  is  always  experienced  in  the  differentiation  of  tuber- 
culosis of  the  lymph-glands  from  true  lymphomata,  and  it  is  rarely  possible 
(except  when  a  gland  has  been  extirpated  and  examined)  to  decide  this  ques- 
tion with  certainty.  As  points  of  support  for  a  probable  diagnosis  the  fol- 
lowing may  serve :  Tuberculosis  of  the  glands  is  rare  in  those  bej^ond  the 
twenty-fifth  year  of  life.  The  appearance  of  glandular  enlargements  without 
any  other  symptoms  in  later  life  would  therefore  be  evidence  against  the 
tubercular  nature  of  the  affection.  Pain  and  tenderness  in  the  enlarged  glands 
is  frequently  observed  in  tuberculosis;  it  is  rare  or  does  not  occur  at  all  in 
lymphomata.  Tuberculosis  of  other  organs  is  greatly  in  favor  of  the  assump- 
tion of  a  glandular  tuberculosis,  and  also  fever,  which,  as  I  have  already  said, 
is  certainly  absent  or  appears  very  rarely  in  the  non-tubercular  form.  En- 
largement of  the  spleen,  in  the  absence  of  fever,  is  against  tuberculosis. 
Finally,  tubercular  lymph-gland  enlargements  adherent  to  their  surroundings 
usually  break  down  from  caseation,  and  if  they  are  superficially  situated  rup- 
ture externally.  In  a  case  of  this  kind  it  is  easy  to  make  the  diagnosis.  But 
caseation  and  abscess  formation  do  not  occur  at  the  onset,  but  only,  if  at  all, 
after  a  lapse  of  time;  hence  until  this  happens  this  criterion  for  diagnosis  is 
not  present.  Apart  from  this  there  is  a  form  of  glandular  tuberculosis  which 
leads  to  very  slight  caseation  or  none  at  all ;  I  refer  to  the  indurative  form. 
The  nature  of  such  cases  is  obviously  difficult  to  determine. .  In  short,  the 
differentiation  of  tubercular  adenitis  from  lymphoma,  or  the  so-called  lymph 
adenomata,  is  very  frequently  difficult  or  impossible  during  life. 


HODGKIX'S   DISEASE  377 

The  same  is  true  of  the  third  previously  mentioned  form  of  glandular 
enlargement,  lympho-sarcomatosis.  According  to  Yirchow,  a  hard  and  a  soft 
form  of  lympho-sarcoma  have  been  differentiated,  depending  upon  whether  or 
not  the  proliferation  of  the  reticulum  of  the  gland  and  of  the  connective  tissue 
predominates  over  the  cell  proliferation.  The  softer  forms,  however,  show 
gradual  transition  stages  to  the  pure  lvmphomata  or  lymphadenomata,  so  that 
even  for  the  pathologist  the  decision  between  these  varieties  of  tumors  may 
be  very  difficult.  Hence,  the  harder  composition  of  the  lymphosarcomata,  com- 
pared to  the  lvmphomata,  has  very  little  diagnostic  importance,  as  the  differ- 
ence is  not  decisive.  Somewhat  more  valuable -in  diagnosis  is  the  fact  that 
lymphosarcoma  has  a  greater  tendency  to  invade'  the  capsule  of  the  gland 
and  the  neighboring  tissue,  and  to  rupture  through  the  skin,  which  never 
occurs  in  pure  lvmphomata,  but  which  does  occur,  as  has  just  been  stated, 
in  tubercular  adenitis.  The  tendency  to  metastasis,  which  has  been  mentioned 
as  characteristic  of  lymphosarcoma,  is  of  very  slight  value  in  diagnosis  during 
life,  for  three  reasons:  First,  adenitis  of  other  types  readily  causes  metastases 
in  internal  organs,  either  by  way  of  the  lymph  stream  or  blood  channel:  sec- 
ondly, metastases  arc  frequently  not  recognizable  by  symptoms;  and  thirdly, 
in  the  presence  of  certain  symptoms  it  may  be  difficult,  even  impossible,  to 
decide  whether  these  symptoms  are  due  to  actual  metastatic  tumors  in  an 
organ  or  are  only  caused  by  the  pressure  and  irritation  which  glandular  tumors 
in  the  cavities  of  the  body  exert  upon  a  neighboring  organ.  Thus,  for  exam- 
ple, symptoms  which  point  to  an  affection  of  the  respiratory  apparatus,  dysp: 
nea,  cough,  etc..  may  be  caused  by  metastases  in  the  lungs  or  in  the  bronchi, 
as  well  as  by  pressure  of  enlarged  mediastinal  glands. 

To  all  this  we  must  add  that,  even  in  quite  unquestionable  cases  of  lympho- 
sarcoma, we  find  the  blood-picture  which  Ehrlich  and  Pinkus  have  designated 
as  characteristic  of  pseudo-leukemia  produced  by  multiple  lvmphomata. 

It  will,  therefore,  not  be  looked  upon  as  an  exaggeration  when  1  say  (hat 
only  in  a  sum/I  minority  of  cases  is  it  possible  to  recognize  with  certainty  the 
anatomical  nature  of  the  glandular  enlargements  which  are  the  foundation  of 
the  clinical  picture  of  pseudo-leukemia.     [See  note  on  page  :;;i. — Ed.] 

ETIOLOGY 

Afl  i"  etiology  very  little  has  1 n  determined  with  certainty.  Tin1  affec- 
tion appears  in  childhood  and  in  adolescence,  somewhai   more  frequently  in 

the  male  than  in  the  female  sex.    Occasionally  several  cases  have  I n  noted  in 

the  Bame  family,  for  instance,  among  brothers  and  sisters  or  in  one  of  the 
parents  and  a  child,  and  this  suggests  a  hereditary  or  family  predisposition. 

Not  infrequently  pseudo-leukemia  occurs  in  connection  with  other  dis- 
eases as,  for  example,  malaria,  and  often  in  my  experience,  after  diseases  which 
are  combined  with  an  inflammatory  irritation  of  the  nasal  cavities  and  of  the 
tracheo-bronchial  mucous  membrane,  i.e.,  after  inflammations  of  the  throat, 
measles,  whooping-cough,  influenza  and  the  like.  One  mighl  assume  that 
from  the  areas  of  mucous  membrane  jusl  mentioned  an  irritation  is  exerted 
upon  the  glands  which  causes  enlargement,  but  then  it  remains  unexplained 


378  PSEUDO-LEUKEMIA 

why  these  inflammatory  affections  which  are  so  exceedingly  common  rarely 
cause  much  glandular  enlargement,  and  it  is  also  inexplicable  how  the  enlarge- 
ment of  the  glands  originally  irritated  can  distribute  itself  to  distant  parts, 
and,  finally,  to  all  or  nearly  all  the  glands  of  the  body.  The  irritation  theory 
must  be  supplemented  by  assuming  a  special  predisposition  to  disease  of  the 
lymph-glands,  and  this  view  must  serve  to  elucidate  those  cases  in  which  no 
causal  factor  that  could  produce  irritation  has  preceded  the  glandular  enlarge- 
ment. More  plausible  is  the  view  that  a  poison  is  at  work  in  the  blood,  and 
that  the  glandular  lesions  are  only  symptomatic.  In  the  cases  which  appear 
to  develop  spontaneously  and  without  any  evidence  of  such  a  poison,  it  is 
probable  that  there  has  been  noticed  irritation  from  the  tonsils,  or  from  the 
whole  pharyngeal  mucous  membrane.  Many  years  ago  I  pointed  out  the  fact 
that  the  so-called  "  vestibulum  pharyngis"  was  a  "vestibulum  malorum,"  an 
ante-chamber  by  which  innumerable  pathogenic  agents  found  their  entrance 
into  the  body.  According  to  this  hypothesis,  in  Hodgkin's  disease  a  damag- 
ing agent  finds  its  way  from  the  pharynx  through  the  lymph-glands  into  the 
blood  and  thus  causes  enlargement,  first  in  the  glands  of  the  neck,  and  later 
in  the  others. 

That  in  the  later  stages  of  the  disease  a  deleterious  agent  must  actually 
be  present  in  the  blood,  is  proven  by  the  almost  invariable  implication  of  the 
spleen,  which  of  late  has  very  aptly  been  designated  as  a  lymph-gland  of  the 
blood. 

COURSE,   DURATION  AND  RESULT 

I  have  very  little  to  add  to  what  has  been  said  regarding  the  course,  dura- 
tion and  outcome  of  Hodgkin's  disease.  The  disease  runs  its  course  with 
paroxysms  of  varying  duration;  as  a  rule  it  lasts  from  one  to  five  years,  very 
rarely  longer.  Two  years  is  an  average  duration.  The  usual  outcome  of  the 
disease  is  death,  which  is  the  result  either  of  the  previously  mentioned  pres- 
sure and  stasis,  or  of  an  increase  in  the  anemia,  producing  exhaustion  which 
is  not  infrequently  intensified  by  copious  hemorrhages.  A  termination  in 
recovery  is  exceedingly  rare.  Occasionally,  prior  to  death,  a  transition  into 
true  leukemia  has  been  observed,  with  the  addition,  therefore,  of  characteristic 
blood-changes  to  the  glandular  enlargements. 

THERAPY 

Trent  merit  of  the  fully  developed  disease  is  not  very  effectual,  as  an  actual 
and  permanent  recovery  can  scarcely  ever  be  brought  about,  but,  at  the  most, 
only  a  cessation  in  the  glandular  enlargement  with  more  or  less  prolonged 
improvement  of  the  general  condition.  Whether  early  treatment  accomplishes 
more,  i.e.,  complete  recovery,  is  questionable.  Nevertheless,  an  effort  should 
be  made  to  combat  the  glandular  enlargement  as  early  as  possible. 

For  this  purpose  various  remedies  are  at  our  disposal  to  which  a  certain 
beneficial  effect  cannot  be  denied;  besides  extirpation  of  the  gland. 

Among  the  remedial  agents,  Billroth  has  advised  arsenic  which  has  proved 
most  efficacious.  This  is  given  either  internally,  or,  more  generally,  in  injec- 
tions subcutaneously  or  in  the  parenchyma  of  the  gland.     For  internal  use 


HODGKIN'S  DISEASE  379 

we  give  Fowler's  solution,  one  to  five  drops  once  or  twice  daily,  besf  given 
diluted  with  twice  or  three  times  this  amount  of  ordinary  or  aromatic  water. 
I  believe  arsenious  acid  to  he  even  more  effective,  either  in  the  form  of  the 
pilulae  asiatieae  (  II  Acid,  arsenicos.  0.06,  piperis  nigri  pulv.  1.5.  rad.  liquir. 
pulv.  3.0.  mueilag.  gummi  arab.  q.  s.  ad  pil.  lx)  of  which  one  pill  is  taken 
once  to  three  times  daily  To  avoid  irritating  the  stomach,  these,  like  all 
other  arsenic  preparations,  are  not  to  be  given  upon  an  empty  stomach,  hut 
only  while  eating  or  immediately  after  a  meal.  A  very  serviceable  arsenic 
preparation  is  sodium  cacodylate,  also  known  under  the  name  of  arsycodile, 
which  contains  considerable  arsenious  acid  (nearly  two-third-)  and  is  well 
borne.  The  dose  for  adults  is  0.025  to  0.1,  and  this  is  gradually  increased 
in  pills  (sodium  cacodylate  0.25  to  0.1,  sacch.  et  gummi  arab.  q.  s.  ad  pil.  x.\\ 
daily  one  to  five  pills)  or  for  children  in  solution  (1:15,  according  to  age 
three  to  ten  drops).  After  prolonged  use  of  this  preparation,  in  some  ci  -  - 
a  disagreeable  garlicky  odor  of  the  breath  appears  and  causes  us  to  desisl  from 
its  use. 

Arsenic  act-  more  readily  by  subcutaneous  or  parenchymatous  injections 
(into  the  glandular  substance)  than  by  internal  administration.  Usually 
Fowler's  solution  is  employed  (beginning  with  0.1  and  cautiously  increasing 
even  up  t<>  one  gram)  or  the  solution  of  -odium  arsenite  advised  by  v.  Ziems- 
sen,  of  which  a  somewhat  larger  dose  is  injected.  But  even  here  cacodylic 
acid  i-  to  be  preferred  on  account  of  its  greater  solubility  and  larger  contents 
of  arsenic.  A  Hi  per  cent,  solution  of  sodium  cacodylate  in  sterilized  water  is 
used  for  about  a  week  (one-half  of  a  Pravaz  syringeful  being  injected)  :  it  is 
then  stopped  for  a  few  days,  and  then  resumed,  the  same  dose  being  injected, 
until  gradually,  with  pauses  of  a  few  day-,  the  dose  is  increased  to  an  entire 
syringeful. 

Recently  a  preparation  containing  a  large  quantity  of  arsenic  atoxyl  (ani- 
lidmetarsenite)  ha-  been  advised  by  Walter  Schild,  and  this  seems  to  deserve 
preference  even  above  tin'  cacodylate.  Of  a  solution  of  two  part-  in  ten  of 
water,  two  io  leu  divisions  of  the  hypodermic  syringe  are  injected  and  the 
dose  i-  gradually  increased.  The  injection-  are  almost  painless,  and  ate  well 
borne.  In  the  only  ca-e  of  Hodgkin*-  disease  that  I  treated  by  this  method 
the  re-nit  appeared  to  be  -a i i.-fact ory.  but  the  duration  of  observation  was  too 
brief  to  permit  me  to  -peak  of  a  permanent  success. 

A  good  auxiliary  remedy  in  every  arsenic  treatment  is  formed  by  the  min- 
eral water-  containing  arsenic  and  iron,  those  of  Roncegno,  Levico,  Srebrenica 
(Guber  Bpring),  and  of  Cudowa  (Eugene  spring),  which,  on  account  of  the 
arsenic  they  contain  (and  this  i-  greatest  in  the  Roncegno  water  and  smallest 
in  the  Cudowa  water),  must  be  administered  with  all  the  caution  with  which 
we  prescribe  other  arsenic  preparation-  (therefore  nol  upon  an  empty  stom- 
ach), in  from  one  to  five  tablespoonfuls  for  adults  ami  a-  many  tea-poonfuls 
for  children;  these  waters  are  best  administered  in  milk  or  Seltzer  water. 

Besides,  preparations  of  iodin  have  been  administered  internally  and  used 
a-  inunctions  over  the  enlarged  glands.  Tiny  have,  however,  not  proven  par- 
ticularly serviceable. 

More  effective  are  inunction-  with  potassium  soap  which,  a-  i-  well  known. 


380  PSEUDO-LEUKEMIA 

is  frequently  beneficial  in  scrofulous  glandular  tumors.  Ordinary  green 
soap  (sapo  kalinus  venalis)  or  the  somewhat  more  agreeable  fluid  potassium 
soap  (sapo  kalinus)  may  be  employed;  of  the  former,  according  to  the  size 
and  number  of  the  enlarged  glands,  a  piece  the  size  of  a  cherry  to  that  of  a 
walnut,  of  the  latter  a  teaspoonful  to  a  tablespoonful  and  more,  may  be  daily 
rubbed  into  the  skin  with  a  pellet  of  cotton  until  redness  and  burning  are 
produced,  when  the  rubbing  is  stopped  and  is  not  resumed  until  these  irrita- 
tive symptoms  have  disappeared. 

Since  it  is  often  impossible  to  determine  the  nature  of  the  glandular  swell- 
ing, as  I  have  previously  stated,  it  is  well  to  add  to  the  soap  substances  which 
have  a  more  or  less  specific  action  in  particular  diseases,  for  example,  iodo- 
form in  certain  tuberculous  processes  (and  also  in  many  syphilitic  ones). 
The  potassium  in  the  soap  loosens  the  epidermis  and  the  cement  edges  in  the 
skin,  and  in  this  way  the  direct  entrance  of  iodoform  into  the  diseased  tissue 
is  facilitated.  An  inunction  of  this  kind  that  I  have  used  in  other  affections 
consists  of:  Iodoform  5.0,  sapo  kalinus  and  lanolin  or  unguentum  adipis  lanae 
or  vaselin,  ää  20.0. 

Extirpation  of  the  glands,  in  so  far  as  they  are  susceptible  to  operative 
interference,  is  unquestionably  indicated  in  those  cases  in  which  a  single  gland 
or  the  pressure  of  several  glands  in  this  area  causes  disturbance  or  becomes 
dangerous.  Opinions  differ  as  to  whether  extirpation  is  advisable  at  an  early 
period  when  only  one  or  a  few  glands  are  slightly  affected,  since  the  results  of 
such  early  excisions  have  varied.  Some  observers  believe  that  extirpation  of 
the  glands,  performed  once  or  several  times,  induces  a  slower  course  or  a  long 
cessation  of  the  disease,  while  others,  on  the  contrary,  have  observed  a  more 
rapid  growth  of  the  glands  to  follow.  The  explanation  of  this  variation  may 
be  that  frequently,  besides  the  external  visible  glands  that  may  be  reached, 
others  lie  more  deeply  hidden,  or  cannot  be  reached  by  the  knife  of  the  sur- 
geon, and  the  operative  removal  of  the  former,  perhaps  also  of  others  which  up 
to  that  time  had  not  been  implicated  in  the  morbid  processes,  causes  irritation. 

Early  extirpation,  therefore,  can  only  be  looked  upon  as  an  experiment 
which  may  meet  with  success,  and  this  is  the  more  likely  the  earlier  it  is 
attempted. 

Besides  this  treatment  which  is  especially  directed  to  the  glandular  swell- 
ing we  must  try  by  every  means  to  reduce  the  anemia  and  improve  the  gen- 
eral condition.  Above  all,  the  patients  should  have  the  advantage  of  the  most 
favorable  hygienic  conditions,  nutritious  food,  fresh  air  either  in  the  country 
or  other  suitable  climate,  as  well  as  such  measures  as  are  possible  in  the  indi- 
vidual circumstances  for  stimulating  metabolism  from  the  shin,  such  as  fric- 
tion, baths,  etc. 

All  this  may  be  most  readily  secured  in  properly  chosen  sanatoria.  The 
most  popular  among  these,  probably  on  account  of  their  well-known  effect 
upon  scrofulous  glandular  affections,  are  the  sodium  chlorid  springs  (particu- 
larly  I  he  stronger  suit  springs),  and  especially  the  iodin-  and  bromin-containing 
salt  springs,  such  us  those  at  Hall  in  Upper  Austria,  Krankenheil,  Königs- 
dorff-Justrzemb,  Kreuznach  and  others.  These  springs  are  used  for  bathing, 
for  poultices,  and,  with  necessary  caution,  also  for  drinking. 


BAXTI'S  DISEASE  381 

The  most  useful  remedial  measures  for  the  latter  purpose  are  tonics  and 
roborants,  and  chiefly  the  preparations  of  iron  and  quinin.  Arsenic  when 
properly  used  has  a  tonic  effect,  and  so  improves  the  nutrition  that  if  it  is 
administered  internally  other  remedial  agents  may  be  dispensed  with,  or  sim- 
ply combined  with  arsenic.  Lately  a  combination  with  ferrum  cacodylicum 
in  doses  of  0.25-0.3  gram  daily  has  been  advised  according  to  the  following 
prescription:  Ferr.  cacodyl.  1.0,  Aqu.  cinnam.  25,  of  which  20  to  40  drops 
are  taken  three  times  daily. 

I  need  hardly  say  that  in  every  dietetic  and  drug  treatment  attention  to  the 
digestive  organs  is  of  great  importance,  and  if  these  show  any  disturbance  of 
function,  amelioration  must  here  be  fir.-t  attempted. 

It  is  also  self-evident  that  febrile  conditions  or  possible  complications  are 
to  be  treated  according  to  their  special  indications.  [The  X-ray  treatment  of 
Hodgkin's  disease  seems  at  this  time  to  promise  more  than  any  other.  The 
number  of  cases  is  not  large,  but  the  results  are  often  favorable.  The  technic 
is  very  simple;  the  affected  glands  are  exposed  to  the  X-ray  for  as  Long  a 
period  (every  day  or  every  second  day)  as  the  skin  will  stand  without  sustain- 
ing any  "  blush."  Pressure  symptoms  due  to  substernal  glands  have  thus  been 
very  notably  relieved. — En.  J 

BANTI'S    DISEASE 

We  turn  now  to  the  description  of  the  second  form  of  pseudo-leukemia, 
the  Uenal  or  splenic  variety,  in  which  enlargement  of  the  spleen  is  predomi- 
nant or  apparently  occurs  alone,  i.e.,  without  glandular  enlargement.  I  say 
apparently,  for,  according  to  my  investigations,  the  lymph-glands  are  almost 

always  implicated.     It  is  true  thai  sometimes  the  enlarg -nt  affects  only  the 

deeper  ones,  particularly  those  glands  situated  in  the  abdominal  cavity,  and 
therefore  recognizable  only  at  autopsy.  There  are  numerous  cases,  as  I  have 
mentioned  previously,  in  which  the  spleen  and  Lymph-glands  are  attacked 
simultaneously,  and  these  cases  are  designated  as  pseudo-leukemia  Lymphatico- 
lienalis,  and  constitute  a  transitional  stage  between  the  two  other  form-. 

Aside  from  the  glandular  swelling  and  the  course  of  the  disease  the  clinical 
picture  in  the  Lienal  form  scarcely  differs  from  thai  of  the  lymphatic  form 
(Hodgkin's  disease),  and  the  description  may  consequently  be  brief. 

Besides  the  enlargement  of  the  spleen,  or  even  before  this  becomes  notice- 
able, tin'  earliest  symptom  is  anemia,  and  Gretsel  (Griesinger)  has  therefore 
designated  the  disease  as  "  splenic  anemia."  Bui  this  name  is  not  distinctive 
for,  as  later  researches  have  Bhown,  the  blood  finding  does  not,  or  at  Leasl  qoI 
always,  correspond  morphologically  to  thai  of  simple  anemia.  On  the  con- 
trary, manifold  changes,  particularly  in  regard  to  the  number  and  proportional 
relation-  of  the  Leukocytes,  are  mel  with,  bul  never  such  a  decided  increase  as 
in  leukemia.  At  one  time  the  blood  may,  in  fact,  resemble  simple  chronic 
anemia,  i.e.,  the  number  of  erythrocytes  may  be  more  or  less  decidedly  de- 
creased, the  hemoglobin  to  the  Bame  degree  or  even  more  decidedly  diminished, 
and  the  proportion  of  Leukocytes  to  erythrocytes,  although  varying  nol  mark- 
edly, exceeds  normal  limits.     | The  very  Low  color-index  has  been  especially 


382  PSEUDO-LEUKEMIA 

emphasized  by  Osler. — Ed.]  At  other  times,  with  the  same  relation  of  the 
erythrocytes  and  of  the  hemoglobin,  leukopenia  is  present;  that  is,  there  is 
a  conspicuous  diminution  of  the  leukocytes  below  the  lowest  normal  limits. 
In  still  other  cases  there  is  a  relative  decrease  in  the  polynuclear  neutrophilic 
leukocytes,  which  normally  make  up  about  three-quarters  of  the  leukocytes. 
Sometimes  the  cells  designated  as  lymphocytes  are  predominant,  i.  e.,  a  lym- 
phocytic mia  is  present.  In  conclusion,  a  blood  change  is  found  which  in  some 
respects  resembles  pernicious  anemia;  namely,  nucleated  erythrocytes  of  nor- 
mal or  larger  size  (normoblasts  and  megaloblasts)  are  seen,  and  with  this  an 
increase  in  the  leukocytes,  sometimes  of  the  polynuclears,  sometimes  of  the 
lymphocytes. 

This  latter  blood  composition  is  observed  pre-eminently  in  infancy,  and 
has  been  described  by  v.  Jaksch  as  anemia  infantum  pseudoleukemia.  This 
is  a  pseudo-leukemia  which  has  special  characteristics  in  the  infantile  organ- 
ism. Normally  the  infant's  leukocytes  are  more  numerous  than  those  of  the 
adult,  and  in  the  child  the  lymphocytes  also  are  more  profuse,  and  from  the 
hyperemia  red  marrow  of  the  growing  bones  nucleated  young  erythrocytes 
more  readily  enter  the  circulation.  These  nucleated  erythrocytes,  according 
to  our  present  views,  are  to  be  regarded  as  immature  corpuscles. 

Other  blood  lesions  such  as  poikilocytosis,  increase  of  the  blood  plaques, 
etc.,  are  not  characteristic. 

We  must  not  expect  that  the  same  blood  condition  will  be  present  in  every 
case  and  at  all  times  for,  in  the  first  place,  these  changes  arise  gradually  in  the 
blood  with  an  increase  of  the  anemia,  and  probably  also  with  the  growth  in  the 
spleen,  corresponding  to  the  growth  in  the  glands,  as  in  Hodgkin's  disease. 
Thus,  in  this  malady,  as  in  the  other  form,  periods  of  transitory  improvement 
in  the  condition  occur  and  the  blood  composition  improves.  Further  febrile 
conditions  may  arise  under  the  influence  of  which  the  number  of  leukocytes 
may  change;  for  example,  a  leukopenia  may  give  place  to  a  leukocytosis;  or, 
again,  profuse  hemorrhages  in  the  disease  may  entirely  alter  the  blood  picture 

In  the  splenic  form  of  pseudo-leukemia,  certainly  in  adults,  hemorrhages 
are  even  more  frequent  than  in  the  lymphatic  form,  especially  hemorrhages 
from  the  nose  and  from  the  gastro-intestinal  canal ;  but  there  are  also  hemor- 
rhages from  the  gums,  from  the  skin,  and  from  the  vitreous  body  of  the  eye, 
etc.  [Osier  has  explained  the  gastric  hemorrhages  as  due  to  the  inability  of 
the  stomach  veins  (anastomosing  with  those  of  the  spleen  through  the  vasa 
brevia)  to  empty  themselves  on  account  of  the  cirrhotic  process  which  forms 
part  of  the  changes  in  the  spleen. — Ed.] 

The  urine  is  very  similar  to  that  of  the  lymphatic  form. 

The  implication  of  the  liver  in  splenic  pseudo-leukemia  is  very  interest- 
ing. In  the  lymphatic  form  enlargement  of  the  liver  also  occurs,  due  to  the 
previously  mentioned  metastatic  lymphomata  or  lymphomatoid  formations. 
But  these  lymphomata  are  rarely  of  decided  extent  and  rarely  give  rise  to 
marked  disturbance.  In  the  splenic  form,  however,  the  liver  is  very  fre- 
quently and  conspicuously  involved.  Banti  deserves  credit  for  having  first 
called  attention  to  the  combination  of  pseudo-leuhemic  enlargement  of  the 
spleen  with  cirrhosis  of  the  liver,  and  for  having  remarked  the  causal  connec- 


BANTI'S  DISEASE  ■     383 

lion  between  them;  therefore  quite  properly  this  combination  is  designated 
as  Banti's  disease. 

The  chief  symptom  by  which  cirrhosis  of  the  liver  may  be  recognized  is 
ascites.  Yet  this  may  occur,  as  I  have  seen,  in  pseudo-leukemia  in  which  the 
liver  is  not  attacked,  or  to  but  an  insignificant  extent,  so  that  besides  cirrhosis 
of  the  liver,  to  which  Banti  refers  the  ascites  in  all  cases,  other  causes 
may  be  operative.  As  such  a  cause  I  have  mentioned  displacement  of  the 
lymph  channels  in  the  abdominal  cavity  by  enlarged  lymph-glands,  which, 
especially  if  combined  with  an  anemic  composition  of  the  blood,  and  perhaps 
with  stasis  due  to  the  marked  enlargement  of  the  spleen,  may  give  rise  to 
ascites.  In  some  cases,  disease  of  the  portal  vein  may  possibly  be  the  cause. 
[A  calcified  thrombus  of  the  portal  vein  has  been  found  by  Warthin  in  two 
of  this  disease  (splenic  anemia). — Ed.] 

Banti  reports  that  in  the  disease  named  after  him  the  intima  of  the  portal 
vein  from  the  anastomosis  of  the  splenic  veins  to  the  liver  has  been  found 
covered  with  coarse  plaques  similar  to  the  sclerotic  and  atheromatous  coats 
of  the  aorta.  Ee  assumes  that  toxic  substances  from  the  originally  diseased 
spleen  have  readied  the  portal  vein  through  the  veins  of  the  spleen,  and  later 
reached  the  liver,  thus  causing  the  pathological  changes.  In  two  cases  belong- 
ing to  this  category  upon  which  autopsies  were  held,  and  in  which  neither 
ascites  nor  liver  cirrhosis  was  present  (which,  therefore,  did  not  strictly  rep- 
resent Banti's  disease),  these  changes  were  not  found  either  in  the  portal  vein 
or  in  the  splenic  vein.  They  belong  perhaps  to  a  more  advanced  -taue  of  the 
disease. 

But  even  if  ascites  is  present  the  clinical  picture  deviates  in  many  essential 
points  from  ordinary  hepatic  cirrhosis,  thai  form  known  as  "alcoholic  liver." 
The  enlargemenl  of  the  spleen  in  pseudo-leukemia  is  much  greater  than  in 
the  latter,  and  the  skin  does  not  show  the  grayish  yellow  discoloration  which 
is  so  usual  in  cirrhosis  of  the  liver.  On  the  contrary,  it  is  pale,  as  in  anemia. 
provided  unusual  circumstances  do  not  bring  about  a  darker  pigmentation. 
For  example,  Osier  has  observed  in  some  cases  a  melanotic  discoloration  due 
to  an  old  miliaria.  Furthermore,  the  urine  is  usually  of  a  differenl  compo- 
sition, without  bilirubin  and  urobilin,  provided  special  complications,  such  as 
decided  stasis  due  to  ascites  and  the  like,  are  not   present. 

We  must,  however,  agree  with  Banti  that  in  the  clinical  condition  named 
after  him  the  enlargement  of  the  spleen  is  the  primary  affection  and  not  the 
resuH  of  enlargement  of  the  liver.  In  the  other  cases  of  splenic  pseudo-leu- 
kemia not  associated  with  hepatic  cirrhosis,  it  can  no  Ionizer  be  doubted  that 
the  enlargement  of  the  spleen  is  the  primary  affection  to  which  the  other 
disturbances,  particularly  the  anemia  and  the  abnormal  composition  of  the 
blood,  may  be  attributed. 

The  anatomical  condition  of  the  -picnic  tumor  is  usually  reported  a< 
dependenj    upon  hyperplasia,  hut    microscopic  investigation   -how-  variations 

which   depend    upon   the  extent    to  which   the   pulp  and    the    Malpi^hian   bodies 

as  well  as  the  trabecular  are  implicated  in  the  hyperplasia.     It  appear-,  or  so 
I  conclude  from  a  case  observed  by  me,  that  in  early  cases  only  the  tissu 
the  pulp  is  hyperplastic  owing  to  a  decided  increase  of  the  lymph-cells  in  the 


384  PSEUDO-LEUKEMIA 

reticulum.  Afterward  an  enlargement  of  the  Malpighian  bodies  with  an  in- 
crease in  their  cells  is  observed,  so  that  they  stand  out  as  grayish  white  nodules 
of  the  size  of  a  pea,  having  the  characteristics  of  lymphomata.  Finally,  with 
the  lapse  of  time  the  connective  tissue  proliferates,  the  capsule  of  the  spleen 
becomes  thickened,  the  spleen  itself  hardens  and  is  permeated  by  more  or  less 
tense  connective  tissue  strands  by  which  the  pulp  is  more  and  more  obscured 
or  absorbed.  The  follicles  become  thickened  and  enlarged  and  gradually  lose 
their  reticular  structure  and  cellular  stratification,  being  changed  into  tough 
fibro-cellular  nodules.  At  last  the  normal  structure  of  the  spleen  disappears 
to  a  greater  or  less  degree,  and  only  tough  trabecular  tissue  remains. 

In  this  process,  the  larger  vessels,  the  arteries,  and  particularly  the  veins, 
are  often  found  thickened,  sometimes  also  covered  with  chalk  plates,  such  as 
Banti  observed  in  the  trunk  of  the  splenic  vein  in  cases  complicated  with 
hepatic  cirrhosis. 

The  cause  of  the  enlargement  of  the  spleen,  i.e.,  the  actual  cause  of  the 
disease,  is  unknown.  In  the  relation  of  the  spleen  to  the  blood,  which,  as  I  have 
already  stated,  may  be  compared  to  that  of  the  lymph-glands  to  individual 
areas  of  tissue,  it  may  certainly  be  considered  that  a  deleterious  element  pres- 
ent in  the  blood  exerts  an  irritation  upon  the  spleen.  What  the  nature  of 
this  irritation  is  we  do  not  know.  Specific  bacteria  or  toxins,  which  nowadays 
so  readily  come  into  consideration,  have  not  been  found.  Much  favors  the 
view  that  the  damage  originates  in  the  gastro-intestinal  canal,  and  thence 
reaches  the  blood.  The  circumstance  that  digestive  disturbances,  especially 
diarrhea,  frequently  precede  enlargement  of  the  spleen,  and  the  fact  that 
swelling  of  the  lymph-glands  in  the  abdominal  cavity  is  rarely  absent,  favor 
this  hypothesis. 

From  this  point  of  view  the  assumption  is  certainly  justified  that  the  dis- 
ease of  the  liver  is  not  necessarily  caused  by  enlargement  of  the  spleen,  but  that 
it  is  the  independent  consequence  of  the  same  deleterious  process.  By  this  we 
do  not  intend  to  deny  that  the  abnormally  constituted  blood  which  circulates 
from  the  spleen  to  the  liver  may  cause  pathological  effects.  It  may  be  in  con- 
sequence of  the  simultaneous  action  of  both  poisons — that  of  the  gastro-intes- 
tinal canal  and  that  of  the  spleen — that  the  hepatic  cirrhosis  sometimes  devel- 
ops very  early,  at  other  times  hardly  at  all. 

As  a  contribution  to  our  knowledge  of  the  etiology  of  pseudo-leukemia,  it 
must  be  stated  that  in  a  fair  proportion  of  cases  the  malady  develops  in  the 
course  of  diseases  in  which  enlargement  of  the  spleen  or  a  chronic  splenic 
tumor  already  exists,  or  in  the  course  of  which  it  appears,  e.  g.,  in  malaria, 
syphilis,  particularly  in  that  form  which  occurs  in  children,  hereditary  sypli- 
ilis,  and  in  rickets.  The  characteristic  symptoms  of  the  latter  diseases  grad- 
ually retrograde,  while  the  splenic  tumor  persists  or  even  increases;  anemia 
and  cachexia  become  more  prominent,  and  gradually  the  boundary  line  between 
these  maladies  and  pseudo-leukemia  disappears,  and  it  becomes  impossible  to 
say  where  the  one  begins  and  the  other  ceases. 

The  character  of  the  blood  may  in  such  instances  decide  the  diagnosis, 
particularly  if  the  change  described  by  Ehrlich  and  Pinkus  is  present — or, 
at  all  events,  a  relative  increase  of  the  lymphocytes  with  a  low  count  of  leuko- 


BANTI'S   DISEASE  385 

eytes  such  as  would  exclude  leukemia.  But  I  have  already  mentioned  that 
a  hematological  condition  of  this  kind  is  not  always  present,  even  in  cases  that 
are  to  be  strictly  considered  pseudo-leukemia.  In  these,  another  state  of  the 
hlood  combined  with  a  characteristic  enlargement  of  the  spleen  is  of  impor- 
tance in  the  diagnosis,  namely,  a  simple  high-graded  anemia,  i.  e..  oligocythe- 
mia and  oligochromemia  and  tins  i-  especially  so  if  leukopenia  be  also  present. 

The  recognition  of  splenic  enlargement  in  cases  of  this  kind  can  hardly  I»*1 
difficult,  for  tin-  spleen  early  attains  a  size  that  is  scarcely  ever  seen  except  in 
leukemia.  Its  lower  border  may  reach  anteriorly  to  the  true  pelvis,  to  the 
median  line  and  even  beyond.  The  surface  is  smooth,  and  upon  pressure  the 
organ  is  hut  slightly  or  not  at  all  painful. 

in  the  differential  diagnosis  all  other  hypertrophies  of  the  spleen  musl  he 
excluded,  and  this  is  usually  not  difficult,  for  acute  enlargements  do  not  come 
into  consideration.  The  chronic  enlargements,  including  tuberculosis  and 
amyloid  degeneration,  which  are  somewhat  rare,  may  he  readily  recognized, 
provided  the  etiologic  factors  and  the  condition  of  the  other  organs  are  con- 
sidered. ["Idiopathic"'  splenic  enlargement  with  anemia  very  slight  or 
absenl  and  no  other  Bymptoms  at  all  is  at  times  difficult  to  separate  from  some 
of  the  cases  in  this  group. — Ed.]  The  diagnosis  is  made  with  less  ease  when 
ascites  is  present,  not  because  there  is  any  difficulty  in  determining  the  enlarge- 
ment of  the  spleen,  hut  because  the  question  then  arises  whether  hepatic  cir- 
rhosis is  also  present,  and  whether  this  or  the  enlarged  spleen  is  the  primary 
affection,  i.e.,  whether  Banti's  disease  has  or  has  not  developed.  Here  again 
an  examination  of  the  hlood  will  aid  in  the  decision  provided  the  above-men- 
tioned changes  are  present.  The  enlargement  of  the  spleen  in  primary  hepatic 
cirrhosis  is  never  bo  great  as  in  Banti's  disease,  and.  according  to  my  experi- 
ence, the  appearance  of  the  skin  and  the  condition  of  the  urine  in  the  latter 
affection  are  not  the  same  as  in  hepatic  cirrhosis. 

The  course  and  termination,  and  therefore  the  prognosis  of  splenic  pseudo- 
leukemia, do  not  differ  greatly  in  adults  from  the  lymphatic  variety.  The 
condition  is  different  in  children.  Here  not  infrequently  il  is  possible  to  bring 
ahoiit  a  decided  improvemenl  in  the  anemia  and  in  the  general  condition,  and 
even  a  diminution  in  the  size  of  the  Bpleen.  I  do  not  know  whether  or  not  this 
retrogression  may  be  complete,  hut  in  cases  not  too  fat-  advanced  I  believe  it 
possible.  This  difference  in  the  nature  of  the  disease  in  adults  and  in  chil- 
dren may  depend  upon  the  action  of  the  blood-forming  organs,  particularly  the 
bone-marrow,  which  in  children  Bhows  a  more  vigorous  function.  It  i<  for 
this  reason  that  children  read  more  readily  to  deleterious  agencies,  and  for 
thi~  reason  also  an  improvemenl  i-  more  easily  broughl  aboul  in  children  than 

In  adults. 

In  the  treatment  of  this  form  of  pseudo-leukemia  the  same  factor-  musl 

guide  US  a-  are  decisive  in  the  other  variety,  only  that  here  not  the  enlarge- 
ment of  the  lymph-glands  hut  thai  of  the  Bpleen  is  to  he  combated,  unfor- 
tunately drugs  have  even  less  p  »wer  to  influence  this  process  than  in  the  former 
instance.     There  an-  a  certain  number  of  Bo-called  "  splenic  remedies,"  hut 

the\  owe  their  reputation  chiefly  to  their  efficacy  in  malaria  and  in  the  en- 
largement of  the  Bpleen  dependenl   upon  thi-  disease.     Quinin  i-  to  he  men- 


386  PSEUDO-LEUKEMIA 

tioned  first  among  these  drugs,  then  piperin  and  eucalyptus.  But,  even  in 
cases  in  which  malaria  has  preceded,  they  have  no  effect  upon  the  remaining 
splenic  tumor ;  and,  besides,  these  patients  have  already  taken  quinin,  arsenic 
or  other  remedies  to  a  considerable  extent.  If  not,  arsenic  in  one  of  the  forms 
previously  mentioned  may  be  emplo}red,  at  least  internally,  on  account  of  its 
stimulation  to  metabolism,  and  perhaps  also  because  of  its  power  in  blood  pro- 
duction. Subcutaneously  atoxyl,  which  has  already  been  mentioned,  is  espe- 
cially worthy  of  a  trial.  Parenchymatous  injections  of  arsenic,  of  carbolic 
acid,  etc.,  have  been  resorted  to,  but  as  these  are  not  absolutely  harmless,  and 
are  of  questionable  value,  they  are  not  advisable.  Inunctions  in  the  splenic 
region  are  useless,  nor  have  I  seen  any  benefit  from  massage  or  electricity. 
Somewhat  more  effective,  it  appears  to  me,  is  the  application  of  cold  to  the 
splenic  area,  particularly  in  the  form  of  the  cold  douche,  the  jet  douche  after 
Fleury,  or  the  fan  douche.  These  are  best  employed  while  the  patient  lies 
upon  the  right  side  of  the  body  in  a  warm  bath,  with  the  left  side  of  the  abdo- 
men exposed. 

The  most  certain  means  of  overcoming  the  splenic  tumor  and  (in  so  far  as 
this  is  considered  to  be  actually  the  first  of  the  main  symptoms  of  the  disease) 
to  bring  about  recovery,  is  splenectomy.  But  this  is  neither  so  easy  nor  so 
harmless  as  the  removal  of  the  enlarged  lymph-gland.  Adhesions  of  the  tumor 
to  surrounding  organs  and  marked  hemorrhage  present  great  difficulties  in 
the  operation,  and  endanger  the  life  of  the  patient.  Nevertheless  lately, 
owing  to  improvements  in  technic,  extirpation  of  the  spleen  has  been  success- 
fully accomplished  in  pseudo-leukemia,  and  in  a  number  of  cases  has  brought 
about  the  disappearance  of  the  anemia  and  of  the  cachexia ;  for  what  length  of 
time  is  another  question.  Of  course  success  is  to  be  expected  only  when  the 
disease  has  not  existed  for  too  long  a  time,  and  severe  sequelae,  such  as  cirrho- 
sis of  the  liver,  multiple  lymph-gland  enlargement,  etc.,  have  not  appeared. 

If  ascites  is  present  the  attempt  may  be  made  to  prevent  its  recurrence, 
and  to  bring  about  a  decrease  in  the  size  of  the  spleen,  producing  a  collateral 
circulation  with  the  venous  system  of  the  body,  by  attaching  the  omentum  and 
the  spleen  to  the  abdominal  wall  (after  Talma  or  Schiassi). 

Extirpation  of  the  spleen  in  children  is  less  likely  to  be  considered,  for 
in  them,  as  mentioned,  the  hygienic,  dietetic  and  drug  treatments  are  more 
effectual.  Iodin  and  iron  have  proven  serviceable,  as  well  as  arsenic;  baths 
and  a  change  of  climate  are  to  be  recommended  as  in  the  lymphatic  form. 
The  same  treatment  is  of  course  to  be  employed  in  adults. 


LITERATURE 

Askanazy,  Ziegler's  Beitr.  zur  path.  Anatomie,  Jena,  1888. 

Bonfils,  Societe  med.  d' observation,  Paris,  1856. 

G.  Banti,  "Lo  Sperimentale,"  1894,  1895;  Ziegler's  Beitr.  zur  allg.  Path.,  etc.,  1898, 

xxiv. 
Clarke,  Brit.  Med.  Journ.,  1901,  ii,  p.  701. 
J.  Cohnheim,  Virchow's  Arch.,  xxiii. 
W.  Ebstein,  Bed.  klin.  Wochenschrift,  1887. 


LITERATURE  387 

P.  Ehrlich  and  F.  Pinkus  in  Nothnagel' s  Spec.  Path.,  1901,  vii,  i. 

Fischer,  Arch.  f.  klin.  Chir.,  1897,  lv. 

Freudweiler,  Deutsches  Archiv  f.  klin.  Med.,  1S97,  lxiv. 

Gretsel,  Berl.  klin.  Wochenschrift,  1866,  Nr.  20. 

K.  Grawüz,  Klin.  Pathologie  des  Blutes,  Berlin,  L902,  2  Aufl.,  p.  351  ff. 

R.  v.  Jaksch,  Wiener  klin.  Wochenschr.,  1889,  \r.  '22,  23. 

A.  Jolles,  Zeitschr.  f.  klin.  Med.,  1898,  xxxiv. 
Kundrat,  Wiener  klin.  Wochenschr.,  1893,  Nr.  12,  13. 

J .  H .  Musser,  Transactions  of  the  Association  of  Amer.  Physicians,  1901. 

Osler,  Amer.  Journ.  of  Med.  Sc,  1900,  January. 

Pel,  Berliner  klin.  Wochenschr.,  1885,  1  und  1887,  35. 

.1/.  Reed,  Julius  Hopkins  Hosp.  Reports,  x,  1902,  Nos.  3-5. 

H'.  Schild,  Berliner  klin.  Wochenschr.',  1902,  Nr.  13. 

H.  Senator,  Berliner  klin.  Wochenschr.,  1901,  Nr.  4G. 

Sternberg,  Centralbl.  f.  d.  Grenzgeb.  Med.  u.  Chir.,  1899,  ii. 

Wilks,  Guy's  Hosp.  Reports,  1856,  ii. 

Talma,  Berliner  klin.  Wochenschr.,  1898,  Nr.  38. 

B.  Schiassi,  "Un  nuovo  trattamento  del  Morbo  del  Banti,"  Bologna,  1902. 


THE    HEMORRHAGIC    DIATHESES 

By    M.    LITTEN,  Berlin 

There  is  a  group  of  diseases  in  which  the  essential  symptom  is  a  tendency 
to  more  or  less  extensive  hemorrhage,  which  distributes  itself  over  various 
organs  and  thus  becomes  dangerous  to  life. 

We  designate  this  tendency  to  external  and  internal  hemorrhages,  which 
probably  depend  upon  a  change  in  the  blood  or  in  the  blood- vessels,  or  in  both, 
as  the  hemorrhagic  diathesis.  The  diseases  which  belong  to  this  group,  which 
in  some  cases  resemble  one  another  so  closely  that  it  has  sometimes  been 
thought  possible  to  combine  them  as  one  disease,  were  formerly  designated 
"  scurvy."  But  to-day  there  is  much  diversity  of  opinion  as  to  how  far  this 
division  is  justified. 

In  accordance  with  the  present  state  of  our  knowledge,  the  following 
groups  will  be  considered  separately:  1.  Scurvy;  2.  Hemophilia;  3.  Morbus 
maeulosus  Werlhofii.  But  even  with  these  subdivisions  it  must  be  empha- 
sized that  our  knowledge  does  not  often  permit  a  sharp  separation ;  the  boun- 
daries are  partly  artificial,  being  neither  etiologically  nor  pathologico-anatom- 
ically  defined  with  accuracy. 

SCURVY 

By  scurvy  we  understand  a  general  disturbance  of  nutrition  which  rarely 
occurs  sporadically  but  usually  epidemically,  and  almost  always  under  the  in- 
fluence of  unfavorable,  unhygienic  circumstances,  particularly  that  of  improper 
food ;  it  is  usually  of  insidious  onset  and  slow  course,  and  may  terminate  either 
in  complete  recovery  or  in  death. 

The  disease  is  characterized  by  a  severe  general  cachexia  and  by  a  series  of 
local  disturbances  chiefly  due  to  a  transitory  hemorrhagic  diathesis;  this  may 
present  symptoms  that  completely  coincide  with  those  of  hemophilia,  of  pur- 
pura hemorrhagica,  or  purpura  rheumatica,  but  is  sharply  differentiated  from 
the  first  by  the  fact  that  the  changes  are  hereditary  in  the  former  affection 
and  permanently  present  in  the  individual,  while  in  the  latter  and  in  scurvy 
we  are  always  dealing  with  an  acquired  disease  which  is  generally  transitory, 
and  terminates  in  recovery  or  death,  although  frequently  many  relapses  take 
place. 

HISTORY 

The  history  of  scurvy  is  exceedingly  interesting  and  important,  as  it  dem- 
onstrates i  r  i « > s t  forcibly  the  progress  of  li3rgiene  and  of  scientific  investigation. 
388 


SCURVY  389 

When,  after  the  discovery  of  America,  shipping  acquired  new  interest, 
when  voyages  which  formerly  were  limited  to  the  coasts  of  countries  were 
extended  over  the  open,  wide  sea,  the  brave  seafaring  men  were  confronted 
with  new  and  quite  peculiar  conditions  of  life.  Cut  off  for  many  months 
from  land,  exposed  to  the  mercy  of  the  winds  and  the  waves,  limited  to  the 
narrow  confines  of  their  ship,  where  they  huddled  together  in  large  numbers, 
often  exposed  to  great  hardship,  in  the  choice  of  food  and  drink  they  were 
entirely  restricted  to  that  brought  from  their  homes,  and  particularly  to  such 
food  as  could  he  kept  for  a  long  time.  Frequently  they  were  compelled  to 
Bubsisl  on  food  more  or  less  tainted.  It  is  obvious  that  such  conditions  would 
inevitably  result  in  disease;  and,  great  and  brilliant  as  are  the  discoveries  of 
that  time,  the  great  and  hideous  figure  of  scurvy,  the  disease  which  developed 
from  these  voyages  of  discovery,  and  which  caused  the  failure  of  many  expedi- 
tions, cannot  be  forgotten. 

In  the  year  1498,  when  Vasco  de  Gama  undertook  his  celebrated  voyage 
around  the  Cape  of  Good  Hope,  the  crew  was  attacked  by  scurvy,  and  of  hin 
persons  he  lost  in  a  short  time  more  than  one-third.  We  know  well  the  deci- 
mating character  of  the  disease  which  occurred  in  the  expedition  of  Cartier 
in  1535,  and  in  those  of  v.  Monts,  Pontgrave  and  Poutrincourt  to  Canada 
toward  the  end  of  tin1  sixteenth  century;  in  the  French  expedition  of  Dellon 
to  India;  in  the  journey  of  the  English  fleet  under  Lord  Anson  around  the 
world  (  1  ">  10-1  Til),  in  which  voyage  the  disease  recurred  repeatedly  in  various 
latitudes,  and  380  out  of  öoO  men  succumbed  t<>  the  malady;  in  the  North 
Polar  expedition  <>f  Ellis  (K  16  11  II  )  in  search  of  the  northwest  passage  to 
Budsou  Bay;  in  the  fieel  of  the  English  admiral.  Gleary,  who  in  1780  re- 
turned with  2,400  scurvy  patients,  and  in  other  expeditions. 

The  reports  of  these  expeditions  are  so  definite  that  there  can  be  no  doubt 
of  tin'  identity  «if  the  disease.  We  have  less  information  regarding  the  occur- 
rence of  scurvy  upon  land,  the  first  reliable  report  of  which  dated  about  a 
hundred  years  later,  at  which  time  the  name  scurvy  or  "scharbock"  for  the 
firsl  time  appeared.  Our  knowledge  of  the  occurrence  of  the  disease  in  an- 
tiquity is  very  limited,  although  it  may  be  assumed  that  the  peculiar  condi- 
tions which  favored  the  appearance  of  the  pest,  ;i-  later  investigation  has 
taught,  must  also  have  produced  scurvy  in  earlier  epochs. 

The  best  historical  accounts  of  scurvy  we  owe  to  August  Hirsch,  whose 
description  we  have  mainly  followed. 

He  succeeded,  however,  in  finding  in  old  medical  writings  only  one  form 
of  the  disease  described  which  so  far  corresponds  to  the  picture  <<(  scurvy 
that  their  identity  may  be  assumed;  namely,  in  the  Eippocratic  collec- 
tion, an  affection  described  as  ciAeos  ai/i-anr»/?.  Although  the  disease  des- 
ignated as  --Ayifs  fjLcyaXai  [Magni  lienes]  by  Hippocrates,  Aretseus,  Cel- 
ans, Caelius,  Aurelianus,  Paulus  .Kgineta.  Avicenna  and  others  has  been 
by  some  authorities  taken  for  scurvy,  Eirsch  demonstrates  that  this  disease  waa 
malaria.  Pliny  mentions  two  diseases,  stomatokake  and  skalotyrbe,  the  first 
in  particular  running  it-  course  with  an  affection  of  the  mouth  resembling 
scurvy. 

But  it  is  quite  as  likely  that  this  was  "  stomatite  ulcereuse/'  an  army  dis- 


390  THE  HEMORRHAGIC   DIATHESES 

ease,  as  the  lierba  Britannica  was  used  for  stomatokake  and  skalotyrbe.  Some 
have  considered  oscedo  (a  disease  mentioned  by  Marcellus)  as  probably  scurvy, 
although  the  nature  of  this  affection  is  otherwise  not  known,  and  we  do  not 
know  what  plant  was  meant  by  herba  Britannica. 

The  occurrence  of  scurvy  in  the  Middle  Ages  is  quite  certain.  Several 
descriptions  exist  of  decimating  diseases  which  followed  the  massing  of  great 
armies,  as  during  sieges,  etc. 

Thus,  Jacques  de  Vitry  reports  the  outbreak  in  1218  and  1219,  in  the 
Army  of  the  Crusaders  while  besieging  Damiette,  of  a  disease  in  the  course 
of  which  the  gums  became  gangrenous,  the  extremities  painful,  the  tibia  later 
turned  frightfully  black,  and  the  patients  were  unable  to  eat ;  thus  the  disease 
ran  its  course,  the  patients  suffering  intense  pain  from  which  most  of  them 
were  only  relieved  by  death.  Joinville  explicitly  describes  a  similar  disease 
which  appeared  in  the  army  of  Louis  IX  while  besieging  Cairo  in  1250.  If 
we  can  conclude  from  these  descriptions  that  the  disease  was  scurvy,  we  may 
also  assume  that  this  disease  had  certainly  occurred  previously. 

Cordus  was  the  first  to  use  the  term  "  scharbock  "  for  this  malady.  But 
Hirsch  believes  it  questionable  whether  he  himself  ever  observed  the  disease. 
On  the  other  hand,  quite  accurate  descriptions  are  given  by  Olaus,  Magnus, 
Echthius,  Eonsseus,  Wierus,  Dodona?us,  and  Brucams.  Most  of  these  ac- 
counts refer  to  epidemics  that  occurred  in  northern  countries  bordering  on 
the  sea,  in  North  Germany,  Scandinavia,  and  The  Netherlands.  From  these 
descriptions  it  also  appears  that  the  disease  usually  occurred  under  circum- 
stances of  great  stress,  such  as  famine,  war,  sieges  or  other  unfavorable  social 
conditions.  Descriptions  of  certain  diseases  as  scurvy,  to  which  their  symp- 
toms show  only  a  partial  similarity,  are  unreliable.  This  is  the  case  with  an 
epidemic  which  is  said  to  have  occurred  in  the  year  1186  in  Saxony,  Thuringia, 
and  some  neighboring  countries. 

The  earliest  description  of  scurvy  by  Fabricius,  rector  of  the  princely 
school  of  Meissen,  is  found  at  the  beginning  of  the  eighteenth  century,  but 
Hirsch  proves  that  the  condition  was  ergotism,  the  nature. of  which  was  still 
unknown  to  physicians  of  that  time.  Medical  history  of  the  seventeenth  cen- 
tui-y,  and  especially  that  of  the  eighteenth,  inclines  us  to  believe  that  during 
this  entire  period  Europe  was  afflicted  with  scurvy  which  was  more  prevalent 
than  any  other  disease.  The  fact  that  during  so  long  a  period  of  time  a  single 
disease  should  have  predominated  to  such  a  marked  extent  is  at  once  sus- 
picious, and  close  investigation  has  shown  that  the  exact  opposite  was  really 
the  case;  that  persons  who  had  rarely  seen  scurvy  declared  almost  everything 
to  be  scurvy,  and  thus  brought  about  tremendous  confusion  in  medical  sci- 
ence. The  cause  of  this  must  be  ascribed  to  Eugalenus,  whose  book,  "  De 
morbo  scorbuto  liber,"  which  appeared  in  the  year  1  720,  Hirsch  declared  to 
be  patchwork  which  could  not  lie  equalled  in  medical  literature,  either  in  the 
ignorance  of  its  author,  or  in  the  results  which  it  nevertheless  achieved,  sjnco 
for  more  than  a  century  it  remained  the  canon  regarding  scurvy,  and  the  best 
physicians  of  the  age  were  unable  to  free  themselves  from  its  influence.  The 
ltonk  made  a  great  sensation,  particularly  the  teaching  that  all  children  were 
born  with  a  predisposition  to  scurvy  (Drawitz),  and  that  the  cause  and  root 


SCURVY  391 

of  every  disease  could  be  recognized  in  scurvy  (Bontekoe).  Not  even  Boer- 
haave  was  able  to  rise  entirely  superior  to  these  views,  but  he  was  sufficiently 
critical  to  state  that  the  disease  had,  during  his  time,  appeared  much  more 
rarely  in  The  Netherlands.  Keen  and  earnest  critics  were  not  lacking  who 
not  only  were  opposed  to  the  scurvy  delusion,  but  went  to  the  other  extreme, 
and  denied  absolutely  the  existence  of  scurvy.  Sydenham  with  others  pro- 
tested against  this,  and  asserted  the  rare  occurrence  of  scurvy,  while  Kramer 
furnished  an  accurate  description  of  cases  actually  observed  by  him  in  which 
he  also  declared  that  the  disease  was  least  known  by  those  who  most  frequently 
described  it.  In  the  year  1753  Land's  masterly  treatise  appeared,  which  up  to 
the  present  time  remains  one  of  the  best  descriptions  of  scurvy:  in  this  he 
compared  the  first  accounts  of  the  disease  (which  he  characterized  as  chaos) 
with  the  later  views  maintained  regarding  the  affection,  and  anew  so  accurately 
portrayed  the  clinical  picture  that  it  subsequently  admitted  of  little  change. 

Notwithstanding  Lind*s  proof  that  scurvy  was  not  an  infrequent  disease 
in  the  previous  century,  the  fact  still  remains  that  it  occurred  far  more  fre- 
quently in  the  period  in  which  Lind  wrote  than  in  our  time.  Hirsch  has 
zealously  investigated  these  epidemics,  and  collected  the  records  of  all  others 
occurring  on  land,  from  1556  to  1877,  in  bo  far  as  they  have  borne  the  test  of 
scientific  criticism. 

Although  we  must  admit  that  this  compilation  is  not  a  complete  history  of 
outbreaks  of  scurvy,  since  not  every  pandemic,  and  nol  nearly  all  of  those  lim- 
ited to  a  small  area,  or  occurring  in  a  single  institution,  have  been  described, 
still  it  enables  us  to  draw  conclusions  regarding  the  frequency  of  the  disease, 
it-  geographical  distribution,  and  the  probable  causes  of  its  development.  In 
all  1  L3  epidemics  are  mentioned,  of  which  two  occurred  in  the  sixteenth,  four 
in  the  seventeenth,  thirty-three  in  the  eighteenth,  and  one  hundred  and  four 
in  the  nineteenth  century.  These  figure-  make  it  strikingly  apparent  that  the 
views  of  Eugalenus  and  his  adherent-  were  exaggerated. 

Of  the  epidemics  in  the  course  of  the  previous  century,  that  of  Paris  is 
to  be  particularly  mentioned;  it  occurred  in  1870-71  «luring  the  siege  of  the 
city,  and  spread  owing  to  the  scarcity  of  food.  Among  the  French  troops 
who.  in  18*3  I,  were  held  as  prisoners  of  war  in  Germany,  an  epidemic  occurred 
in  [ngolstadi  which,  however,  according  to  Döring,  did  not  attain  greal  dimen- 
sions; among  1.0,000  prisoners  only  L59  were  attacked.  In  the  Biilbank  Peni- 
tentiary in  London  -curvy  prevailed  in  1824  and  IS  pi;  also  in  the  prison  in 
Prague  in  1831,1836  and  1842;  in  the  workhouse  of  Lndwigsbnrg  in  Württem- 
berg in  four  successive  year-,  from  L850  to  is:,;',,  and  in  the  prison  of  the  Bame 
city,  in  l^:>;.  The  last  epidemic  in  Germany  worth  mentioning  occurred  in 
L875-76  in  a  penal  Institution  in  the  city  of  Moringen;  the  hi-t  in  France  in 
the  -prim:  of  1877  in  the  prison  at  Mazas.  Epidemics  occur  more  frequently 
in  Russia,  even  to-day,  usually  under  the  influence  of  extraordinary  cirennv- 

Btance8,  Buch  a-  crop   failure,   famine,  or  other  social  evil. 

The  majority  of  the  epidemics  in  Birsch's  tabulations  are  found  to  have 
occurred  in  Russia,  and  this  country  also  furnishes  interesting  detail-  regard- 
ing the  geographic  distribution  of  the  disease.  Russia  with  35  epidemics  is 
followed  by  Germany  with   19  epidemics,  France  with   L5,  Sweden,  Norway 


392  THE  HEMORRHAGIC  DIATHESES 

and  Denmark  with  14,  and  England  with  11.  The  other  European  countries 
present  much  smaller  figures.  Of  foreign  countries  India  heads  the  list  with 
14  epidemics,  then  follows  North  America  with  17,  and  Algiers  with  7.  The 
disease  may  even  to-day  he  looked  upon  as  endemic  in  Eussia,  and  occasionally 
it  shows  extraordinarily  wide  distribution,  as  is  evident  from  the  reports  of 
the  Obuchow  Hospital  in  St.   Petersburg. 

In  the  great  epidemic  of  1849  which  distributed  itself  over  a  wide  area  of 
the  Eussian  Empire,  Krebel  reports  that  among  260,444  persons  60,958  died. 
In  Asiatic  Eussia  also,  especially  along  the  coast  of  the  Arctic  Sea,  in  the 
Siberian-Chinese  boundary  land,  and  upon  the  peninsula  of  Kamchatka,  scurvy 
is  frequently  seen  to-day.  In  northwestern  Europe  scurvy  never  played  a 
prominent  role,  and  although,  for  example,  a  famine  with  scurvy  appeared  in 
Iceland  in  the  years  1836-37,  the  scurvy  did  not  assume  an  endemic  character. 
The  conditions  are  the  same  in  other  European  countries ;  only  now  and  then 
localized  epidemics  are  reported  from  prisons.  Epidemics  have  prevailed  ex- 
tensively in  Algiers  without  assuming  a  distinctly  endemic  character;  scurvy 
appeared  among  the  French  troops  in  Egypt  in  1801 ;  in  Abyssinia  the  disease 
has  been  observed  almost  exclusively  in  travellers,  the  natives  being  spared, 
although  they  usually  live  under  decidedly  more  irnfavorable  and  insanitary 
conditions  than  the  strangers,  and  these  conditions  are  powerful  factors  in  the 
distribution  of  the  disease.  On  the  other  hand,  in  the  Eastern  Soudan  and 
in  the  entire  rain  zone  of  East  Africa  the  disease  is  said  to  occur  frequently 
among  natives  as  well  as  strangers.  In  South  Africa,  on  the  contrary,  the 
disease  is  reported  to  be  quite  unknown  among  the  negroes. 

In  Asia,  India  in  particular  is  subject  to  the  disease;  a  great  number  of 
epidemics  there  are  reported ;  these  occurred  chiefly  among  the  poorer  popula- 
tion, and  were  widespread.  Upon  the  coast  of  Dschemenia  (Arabia)  the  dis- 
ease is  endemic;  in  1839  the  English  troops  in  Aden  were  attacked  by  it;  in 
China,  especially  in  the  northern  provinces  in  which  the  population  live  in  a 
squalor  elsewhere  unequalled,  epidemics  are  not  rare;  also  among  the  poorer 
population  in  Japan  scurvy  is  quite  frequent. 

In  Australia,  in  numerous  expeditions  to  the  interior  which  were  under- 
taken for  purposes  of  discovery,  the  affection  has  been  very  serious,  and  lately 
it  has  appeared  endemically  among  the  shepherds  upon  the  wide  grazing  plains 
of  that  country. 

In  the  southern  parts  of  America  the  disease  appears  to  be  unknown, 
and  in  the  north  the  natives  show  no  susceptibility  to  the  affection.  The  epi- 
demics which  have  been  reported  occurred  among  United  States  troops  who 
were  exposed  to  great  privations  at  outlying  stations,  in  lumber  camps  in  the 
interior  of  Canada,  but  particularly  in  California  during  the  gold  fever,  among 
adventurers  who  had  collected  from  all  parts  of  the  earth  and  who  lived  under 
circumstances  of  great  privation.  These  reports  now  have  renewed  interest 
because  great  numbers  of  people  have  rushed  to  the  gold  fields  of  Alaska, 
where,  after  Greenland,  scurvy  is  more  prone  to  occur  than  in  any  country  of 
the  Arctic  regions,  and  where  all  the  conditions  are  favorable  for  the  outbreak 
of  an  epidemic. 

Among  the  members  of  the  well-known   Nansen  expedition,  from  July, 


SCURVY  393 

1893,  to  August,  1896,  which  was  one  of  the  most  important  voyages  of  scien- 
tific investigation  of  all  times,  not  a  single  case  of  this  disease  occurred. 
Later,  when  considering  the  prophylaxis,  we  shall  refer  to  the  important  meas- 
ures by  which  the  celebrated  leader  prevented  an  outbreak  of  the  disease 
which  might  have  brought  the  expedition  to  an  end. 

An  important  American  investigation  of  scurvy  in  children,  in  the  year 
1898  (the  American  Pediatric  Society's  Collective  Investigation  of  Infantile 
Scurvy  in  North  America),  has  given  the  following  results:  Of  372  cases, 
.'!•;;  occurred  in  the  white.  4  in  the  black  race,  and  1  in  the  Chinese;  51  per  cent. 
were  males,  L9  per  cent,  were  females.  The  greatest  number  of  cases  occurred 
between  the  seventh  and  fourteenth  mouths.    We  shall  refer  to  this  again. 


ETIOLOGY 

In  spite  of  many  endeavors  it  has  been  impossible  to  discover  a  cause 
which  can  be  considered  at  all  reliable;  all  search  for  the  pathogenic  agent 
of  the  disease,  though  it  is  often  assumed  to  be  of  miasmatic,  or  even  of 
infectious  origin,  has  been  without  result. 

The  question  of  food  remains  the  alpha  and  the  omega  in  the  etiology  of 
scurvy,  as  in  so  far  as  the  food  supply  is  influenced  by  the  conditions  of  weather 
and  the  seasons  the  latter  will  always  have  a  more  or  less  decisive  influence  in 
the  production  of  the  disease. 

It  is  generally  assumed  thai  improper  nutrition  in  a  certain  direction  is 
pre-eminently  responsible  for  the  affection,  particularly  a  deficiency  of  vege- 
table acid  potash  in  the  daily  food.  It  has  repeatedly  been  noted  that  during 
long  sea  voyages  in  which  salted  or  pickled  meat  exclusively  was  consumed 
Bcurvy  appeared.  As  the  ash  of  pickled  meat  contains  much  Less  potassium 
than  that  of  fresh  meat,  an  attempt  lias  been  made  to  ascribe  scurvy  to  the 
deficienl  intake  of  potassium,  but  perhaps  quite  improperly  so.  for  in  prisons 
where  the  diet  consists  almost  exclusively  of  vegetables  rich  in  potassium, 
scurvy  is  not  infrequently  noted.  On  the  other  hand,  it  has  been  remarked 
tbat  many  race-  in  the  far  north  are  often  compelled  for  month-  continuously 
to  Live  on  pickled  meal  or  salted  fish  without  being  attacked  by  scurvy. 

Later  investigations,  in  which  an  amelioration  of  the  scorbutic  affection 
is  -aid  to  have  followed  the  addition  of  fat  to  the  diet,  appear  to  indicate 
thai  -cur\y  is  due  rather  to  ;i  diel  limited  in  variety  and  deficient  in  fat  than 
to  a  lessened  amounl  of  potassium  salts  in  the  food. 

Bi  sides  tbi-.  a  number  of  other  causes  are  considered  to  be  active:  Gen- 
eral deficiency  in  food,  the  close  huddling  of  many  persons  in  cramped,  unclean 
and  wel  dwellings,  excessive  corporeal  labor  and  psychical  depression,  and. 
above  all.  the  ingestioD  of  tainted  food  (ptomain  poisoning). 

In  considering  more  minutely  the  factors  which  are  mentioned,  we  mu-t 
fir-t  consider  the  view  thai  scurvy  is  ;i  miasmatic  or  infection-  disease. 

The  lii'-t  experimental  investigations  of  this  Bubjecl  were  made  by  Mum 
in  Bologna,  who  injected  Bubcutaneously  rabbits  with  blood  taken  from  scurvy 
patient-.  A  rise  in  temperature  and  small  petechias  developed  in  the  Lobes 
of  the  ears  of  these  animal-.     Upon  killing  the  animals  hemorrha 


394  THE   HEMORRHAGIC  DIATHESES 

also  found  in  the  serous  membranes  and  in  the  internal  organs.  Murri  quite 
properly  avoids  drawing  conclusions  regarding  the  transmissibility  of  the  dis- 
ease from  these  results.  Analogous  findings  were  obtained  by  Contü  and 
Mari  in  similar  experiments.  Further  investigations  resulted  in  the  cultiva- 
tion of  the  pathogenic  agent  of  the  disease  from  the  blood  of  scurvy  patients. 
Wieruszskij  obtained  from  scurvy  blood  in  numerous  cultures  on  various 
media,  partly  negative  results  and  partly  well-known  bacteria,  so  that  he  con- 
cluded that  scurvy  could  not  be  regarded  as  an  infectious  disease  due  to  micro- 
organisms which  could  be  found  in  the  blood.  Babes  conducted  further  ex- 
periments. He  started  with  the  presumption  that  scurvy  is  an  infectious 
disease,  and  that  the  point  of  entrance  for  the  pathogenic  agent  must  be 
sought  for  in  the  mucous  membrane  of  the  alveolar  processes.  He  therefore 
extirpated  small  portions  of  the  gums  of  scurvy  patients,  and  in  the  prepara- 
tions which  had  been  hardened  in  alcohol  he  demonstrated  a  definite  bacillus 
with  which  he  infected  rabbits  by  intravenous  injection.  Hemorrhagic  foci 
occurred  in  various  organs  in  which  the  bacillus  was  also  found.  Babes  de- 
scribes the  bacillus  as  an  elongated,  bent  organism,  pointed  at  the  ends,  about 
0.3  fi  wide  and  of  about  the  same  length,  often  forming  waving  threads  twice 
as  long  and  of  various  lengths,  somewhat  thinner  and  decidedly  longer  than 
the  cholera  bacillus.  The  youngest  specimens  are  double  structures,  and  show 
the  tendency  to  form  metachromatic  bodies  which  stain  dark  violet  with 
methylene-blue,  and  are  thicker  than  the  rods.  The  rods  themselves  stain 
only  weakly  with  rubin,  and  do  not  stain  according  to  Gram.  The  bacilli 
resemble  the  bacillus  e  described  by  Miller,  and  are  probably  always  present 
in  the  oral  cavity.  The  investigations  of  Babes  certainly  require  further 
confirmation,  for  they  are  assuredly  open  to  doubt.  He  himself  admits  that  he 
has  not  found  the  pathogenic  agent  of  scurvy,  but  only  speaks  of  a  "  bacillus 
that  causes  gingivitis  and  hemorrhages  in  scurvy."  The  findings  of  Bosenell 
and  Bornträger  are  quite  unreliable;  the  latter  does  not  even  consider  the 
cocci  found  by  him  as  the  pathogenic  agent  of  scurvy. 

Jackson  and  Harlcy  x  regard  scurvy  as  a  ptomain  poisoning.  To  prove 
this  view  experimentally  they  have  attempted  to  produce  scurvy  in  monkeys 
by  feeding  them  with  tainted  meat.  Some  of  the  animals  had  rice  and  maize 
given  to  them  with  fresh  meat ;  a  second  group  was  fed  on  the  same  food 
except  that  the  meat  was  tainted  by  prolonged  standing;  a  third  group  ate 
the  same  food  as  the  second  with  the  addition  of  fresh  fruits.  Prolonged 
observation  of  the  animals  gave  the  following  results:  The  first  group  of  ani- 
mals showed  no  characteristic  symptoms  except  slow  emaciation  and  diarrhea 
which  appeared  after  some  time.  The  monkeys  of  the  second  group  showed 
decided  diminution  in  strength,  and  in  the  majority  of  them  there  was  a 
mueo-hemorrhagic  diarrhea  as  well  as,  in  some  of  them,  spongy,  bleeding,  and 
ulcerative  gums.  In  two  of  these  animals  the  blood  examination  revealed  a 
decided  decrease  of  hemoglobin  with  a  slight  decrease  in  the  number  of  erythro- 
cytes and  marked  leukocytosis;  a  decrease  of  specific  gravity  dependent  par- 
ticularly upon  a  diminution  of  proteids;  increase  of  fibrin  and  of  coagulabil- 

i  "  An  Experimental  Inquiry  into  Scurvy."     Lancet,  April  28,  1900. 


SCURVY  395 

ity;  therefore,  in  the  main,  a  picture  which  resembled  the  anemia  of  human 
scurvy.  The  authors  mentioned,  therefore,  believed  themselves  justified  in  de- 
claring the  disease  of  the  monkeys  to  be  scurvy,  although  the  autopsies  estab- 
lished no  proof.  In  the  third  group  the  addition  of  fresh  fruits  but  slightly 
influenced  the  disease  of  the  animals.  These  investigations,  although  requir- 
ing further  demonstration,  may  be  looked  upon  as  proof  that  contaminated 
meat  has  deleterious  effects  even  in  monkeys  and  as  confirmation  of  the  prac- 
tical experience  that  only  the  intake  of  fresh  meat  can  prevent  the  outbreak 
of  scurvy  (compare  prophylaxis). 

These  investigations  in  connection  with  recently  expressed  views  as  to  the 
importance  of  oral  affections  in  the  development  of  pernicious  anemia  (  ?)  led 
Eome  '  i"  assume  that  an  affection  of  the  gums  is  the  origin  of  scurvy.  He 
believes  that  microorganisms  still  unknown  (which  may  develop  from  tainted 
food)  infect  the  digestive  tract,  first  producing  a  disease  of  the  gums,  and 
then  an  anemia  which  leads  to  hemorrhages  and  ulceration.  Outbreaks  of 
scurvy  occurring  under  circumstances  which  preclude  cleanliness  of  the  oral 
cavity  are  in  conformity  with  this  theory. 

Turner,2  according  to  the  data  gathered  by  him  during  the  great  scurvy 
epidemic  in  the  eastern  provinces  of  Russia  during  the  year  1899,  believes 
scurvy  to  be  due  to  a  specific  pathogenic  agent  which  is  still  unknown,  and  to 
be  an  infectious  disease  which  is  transmissible  by  contagion.  In  this  he  rea- 
sons only  from  a  clinical  standpoint,  whereas  bacteriologic  investigations  in 
tbi-  epidemic  have  given  no  positive  results.  The  foundations  for  his  belief 
thai  the  disease  results  from  infection  and  not  from  errors  in  diei  are:  1.  The 
epidemic  character  <>f  the  disease;  2.  Its  appearance  in  definite  localities  while 
neighboring  districts  or  those  with  which  there  is  but  Blight  communication 
remain  free;  3.  The  frequency  of  the  disease  among  the  rich:  4.  The  com- 
mon occurrence  of  the  disease  in  persons  who  are  in  daily  contact  with  the 
patients.  Ee  relates  his  experience  with  these  conditions  in  a  collection  of 
villages  in  the  Government  of  Kazan  which  are  populated  by  various  races 
(Russians,  Tartars,  Tchuktchis),  living  isolated  from  each  other.  While  the 
Russian  villages  remained  almost  free  from  the  disease,  the  villages  in  which 
there  was  hut  little  communication  with  other  races  showed  many  cases  of  (lie 
affection,  particularly  among  the  rich  Tartar  population.  But  in  this  region, 
a  village  in  which  very  poor  heathen  Tchuktchis  lived  entirely  isolated  re- 
mained uninfected.  The  fact  that  the  Tartars  and  their  relatives  ate  salted 
meat  almost  exclusively  and  no  vegetables  is.  in  hi-  opinion,  not  proof  to  the 
contrary.  He  lays  the  greatest  Btress  upon  the  cases  in  which  the  disease  was 
contracted  through  nursing;  among  eight  nurses  who  were  active  there,  four 
«civ  attacked,  and  even  the  author  himself  had  a  mild  form  of  the  disease. 

The  previously  mentioned  collective  American  Report  -how-  that  so-called 
infantile  scurvy  nni-t  he  regarded  a-  the  consequence  of  a  chronic  intoxica- 
tion   (chronic  ptomain   poisoning)    produced   by  unsuitable   food,   for  which 


i "The  Etiology  of  Scurvy."    Lancet,   \uimi-i  i.  1890. 

-  ••  I..'  Scorbul  es1  il  une  maladie  iniectieuse  ou  contagieuse  T  "    Arch.  ptfndr.  <l<    I/«./., 

A. nit,   l'JOU. 


396  THE  HEMORRHAGIC  DIATHESES 

intestinal  fermentative  processes  have  prepared  the  way.  In  167  of  372  chil- 
dren in  the  first  year  of  life,  scurvy  was  preceded  by  another  disease,  usually 
disturbance  of  the  digestive  organs.  The  nutrition  prior  to  the  appearance 
of  scurvy  had  consisted  in  10  children  of  breast  milk  exclusively,  in  4  of  unster- 
ilized,  in  68  of  sterilized,  milk,  and  in  the  remainder  of  artificial  foods. 

We  shall  now  consider  what  other  factors  may  also  be  regarded  as  causes 
of  this  disease. 

It  is  certain  that  age  and  sex  do  not  play  a  role  in  scurvy,  although  it  has 
been  erroneously  maintained  that  in  single  epidemics  particularly  persons  of 
a  definite  age,  or  of  one  sex,  have  been  attacked  (for  example,  according  to 
Fauvel,  in  the  Salpetriere  in  Paris  in  1847  only  old  women  had  the  disease). 
Scurvy  occurs  more  frequently  in  men  than  in  women;  the  reason  for  this 
is  quite  obvious,  for  it  is  men  who  are  chiefly  exposed  to  the  causes  of  the 
disease. 

The  same  circumstances  make  it  apparent  why  the  disease  usually  appears 
during  middle  life,  but  no  age  can  be  said  to  be  exempt,  as  the  disease  has 
been  noted  in  the  aged,  occurring  epidemically,  and  also  in  foundling  asylums 
which  were  improperly  conducted.  The  so-called  infantile  scurvy  occurs  in 
nurslings  in  the  first  year  of  life,  particularly  in  the  ninth  and  tenth  months ; 
it  has  so  far  been  impossible  to  determine  that  any  particular  variety  of  food 
is  the  cause;  breast-fed  children  are  affected  as  well  as  those  brought  up  on 
sterilized  cow's  milk  or  artificial  foods.  It  has  lately  been  maintained  of 
Barlow's  disease  that  milk  which  has  been  cooked  too  long,  or  that  which  has 
been  subjected  to  too  high  a  temperature,  may  be  the  cause.  Those  who  adhere 
to  this  view  may  easily  assign  the  same  cause  for  infantile  scurvy. 

It  has  been  shown  in  most  scurvy  epidemics  that  individual  predisposition 
plays  a  certain  role  as  well  as  the  constitution  of  the  patient.  It  is  unques- 
tionable that  persons  who  have  recently  recovered  from  other  diseases,  or  are 
still  suffering  from  them,  are  particularly  liable  to  an  attack  of  scurvy.  As 
predisposing  diseases  we  may  mention  malaria,  dysentery,  enteric  fever,  tuber- 
culosis, trauma  as  well  as  syphilis,  especially  after  a  very  active  mercurial 
treatment  (Krebel).  It  is  needless  to  enumerate  all  of  the  predisposing  dis- 
eases, but  I  should  like  to  point  out  that  I  have  repeatedly  observed  isolated 
cases  of  severe  scurvy  in  immediate  connection  with  influenza.  Quite  recently, 
too,  I  treated  three  cases  of  the  severest  form  of  scurvy,  two  fatal  cases  in 
female  children  of  thirteen  and  fifteen  years,  in  whom  the  disease  was  con- 
nected with  measles  and  tuberculosis,  the  third  case  in  a  diabetic  aged  sixty- 
four.  Moreover,  I  should  like  to  emphasize  that  occasionally  cases  of  scurvy 
with  very  extensive  cutaneous  hemorrhages  and  intense  oral  implication  occur 
in  absolutely  healthy  and  well-nourished  individuals,  living  under  the  most 
favorable  circumstances,  in  whom  not  one  of  the  recognized  causes  can  come 
into  question  at  all.  Such  obscure  and  entirely  incomprehensible  cases  con- 
vince us  that  up  to  the  present  time  we  have  no  absolute  knowledge  regarding 
the  cause  of  the  disease;  they  make  it  probable, however, that  we  should  consider 
the  view,  sometimes  expressed  and  constantly  rejected,  that  predisposition  to 
scurvy  may  be  hereditary,  even  though  to-day  a  discussion  of  this  question 
does  not  appear  to  be  timely.     The  facts  mentioned  have  nevertheless  been 


SCURVY  397 

proven  beyond  doubt,   and  I   could  cite  other  typical  and  convincing  cases 
from  my  own  experience. 

That  a  particular  climate  cannot  he  considered  etiologically  is  evident 
from  the  geographical  distribution  of  the  disease.  Great  stress  has  been  laid 
upon  the  prevalence  of  damp,  cold  weather  during  the  time  of  epidemics,  yet 
it  appears  from  numerous  communications  that  in  winter  and  in  summer,  with 
a  moist  as  well  as  with  a  dry  air.  the  disease  has  been  widely  distributed.  The 
conditions  of  the  soil  have  little  absolute  importance. 

According  to  our  present  knowledge  the  disease  appears  to  be  induced  by 
unhygienic,  above  all  by  improper  alimentary,  conditions.  The  enumeration 
of  these  and  the  history  of  the  disease  show  that  by  far  the  greatest  number 
of  epidemics  have  occurred  upon  long  sea  voyages,  in  camps,  in  besieged  for- 
tresses, in  barracks,  in  prisons,  in  almshouses,  in  foundling  asylums,  etc. 
Under  such  circumstances  a  great  number  of  injurious  factors  ad  conjointly. 
and  it  is  a  question  to  which  of  these  the  greatest  importance  is  to  be  attached. 
Besides  insufficient  clothing,  contaminated  air  as  tin1  result  of  over-crowding  of 
rooms,  and  other  influences  that  take  part  in  the  etiology  of  the  disease,  there 
is  great  unanimitv  among  observer-  of  all  times  and  count  tie-  a-  to  the  decided 
influence  of  faulty  nutrition  in  the  causation  of  scurvy.  However,  the  views 
diverge  widely  as  to  what  errors  in  diet  are  most  important.  Scurvy  has  sel- 
dom occurred  after  a  famine,  although  very  frequently  alter  a  failure  of  crops. 
On  the  contrary,  it  ha-  been  attributed  to  the  almost  exclusive  use  of  salt 
meat;  this  was  the  prevailing  opinion  before  modern  method-  of  preserving 
made  it  possible  to  supply  better  food  to  ships,  and  at  a  period  when  sea  voyages 
were  much  longer  than  at  present,  SO  that  a  crew  for  months  at  a  time  sub- 
sisted exclusively  on  meat  which  had  been  salted.  .Many  races  in  the  far 
north,  however,  year  in  and  year  mit.  live  almost  wholly  upon  salt  meat  and 
fish,  and  in  spite  of  this  scurvy  is  almost  unknown  among  them:  numerous 
observers,  too,  have  reported  epidemic-  in  which  there  was  absolutely  no  de- 
ficiency of  fre-h  meat.  The  lack  of  fresh  water  has  also  been  mentioned,  but 
only  in  isolated  cases  (the  report  of  Beckler  of  the  expedition  of  Burke  to  the 
interior  of  Australia  in  L861  ). 

The  number  of  observations  -bowing  the  importance  of  a  deficiency  of 
fresh  vegetables  in  the  food  is  almost  overwhelming.     We  regrei   we  cannot 
enter  into  the  detail-  of  these,  hut  refer  the  reader  to  Hirsch,  who.  in  a  "  -lmrt 
compilation  to  which  he  devotes  many  pages,  relate-  the  full  particulars. 

We  shall  only  briefly  -täte  that  Bachstrom  was  the  first  to  point  out  the 
influence  of  a  deficiency  of  fre-h  vegetables  in  the  food.  Lee  tell-  u-  that 
the  severe  epidemic  in  L823  in  the  Bouth  of  Russia  began  when  greal  Bwarms 
of  grasshoppers  devastated  the  fields.  Almost  all  the  report-  of  the  epidemic 
of  Bcurvy  during  the  siege  of  Paris  in  1870  "I  agree  in  stating  that  it  devel- 
oped only  when  the  supply  of  fresh  vegetables,  especially  of  potatoes,  was  ex- 
hausted, in  spite  of  tin'  unhygienic  and  evil  social  condition-  previously  ex- 
istent. 

Del  I  »ech  cites  the  case  of  a  wine  merchant,  aged  forty- live,  who  wa-  attacked 

by  Bcurvy  alt! gh  living  in  easy  circumstances,  in  a  sanitary,  dry,  ami  well- 
heated   house,  and   partaking  plentifully  of  fresh   meat,  yet    in   hi-  dietary   no 


398  THE  HEMORRHAGIC  DIATHESES 

fresh  vegetables  were  found.  He  recovered  on  eating  vegetables  and  juicy 
fruits.  We  can  rarely  prove  the  post  hoc,  propter  hoc  with  such  certainty  as 
here,  where  the  eating  of  fresh  vegetables,  particularly  those  belonging  to 
definite  categories,  is  the  best  preventive,  and  in  an  existing  scurvy  is  the  best 
remedy. 

The  fact  that  certain  vegetables,  above  all  potatoes,  have  such  a  positive 
action  caused  Garrod  to  note  that  potatoes  in  particular  contain  a  great  amount 
of  potassium  carbonate.  He  then  examined  other  foods  to  ascertain  the 
amount  of  potassium  carbonate  (potash)  which  they  contained.  According  to 
him  they  contain  in  one  ounce  (=  about  30  grams)  as  follows: 

Potatoes,  large  (cooked),  (1  gr.  =  about  0.06  gram) 1 .875  grains 

Potatoes,  small  (raw) 1 .310  " 

Lime  juice 852  grain 

Lemon  juice 846 

Oranges  (unripe) 675  " 

Mutton  (cooked) 673 

Beef  (raw) 599 

Meat,  pickled  (slightly  salted) 572  " 

Peas 529  " 

Beef  (salted).' 394  " 

Onions 333  " 

Wheat  bread 258  " 

Cheese  (Holland) 230  " 

Wheat  flour  (the  best) 100  " 

Oatmeal 054  " 

Rice 010  " 

In  consequence  of  these  investigations  Garrod  supposes  that  a  too  slight 
intake  of  acid  vegetable  potassium  is  the  primal  cause  of  scurvy,  and  cele- 
brated authors,  above  all  J.  v.  Liebig  and  Hirsch,  coincide  with  him. 

The  part  that  the  potato  plays  in  regard  to  scurvy  may  be  recognized  from 
the  fact  of  the  decrease  of  the  disease  with  the  increase  of  potato  culture.  How 
much  the  cultivation  of  vegetables  was  neglected  in  former  times  is  shown  by 
Hirsch's  statement  that  Katharine  of  Arragon,  the  wife  of  Henry  VIII,  in 
order  to  obtain  a  salad,  was  obliged  to  send  her  gardener  to  The  Netherlands 
for  the  material. 

But  scurvy  has  not  developed  exclusively  where  there  was  a  deficiency  in 
vegetables,  and  particularly  those  rich  in  potash.  Hirsch  relates  a  great 
number  of  examples  confirmatory  of  this.  Indeed  no  one  will  now  maintain 
that  other  causes  are  no  longer  to  be  considered;  on  the  contrary,  the  excep- 
tions prove  that  a  great  predisposing  impprtance  may  be  attached  to  them. 
We  may  perhaps  suppose  that  in  the  above-mentioned  exceptions  sufficient 
potassium  was  consumed  in  the  food,  but  for  some  reason,  perhaps  as  the 
result  of  other  deleterious  causes,  the  organism  was  unable  to  assimilate  it. 
Bunge  believes  that  a  cause  may  be  found  in  the  immoderate  and  extensive 
use  of  salted  meat,  for  the  reason  that  in  pickling  the  meat  the  salts  and  also 
the  potassium  are  extracted  from  it. 

A.  E.  Wright 1  had  previously  expressed  the  opinion  that  the  disease  de- 

i  "  On  the  Pathology  and  Therapeutics  of  Scurvy."    Lancet,  August  25,  1900. 


SCURVY  399 

fends  upon  a  hind  of  acid  intoxication,  owing  to  the  fact  that  the  diet  which 
experience  shows  is  a  cause  of  scurvy  contains  a  great  excess  of  mineral  acids 
in  comparison  with  the  bases.  This  agrees  with  the  fact  that  antiscorbutic 
remedies  in  general  contain  a  superfluous  amount  of  bases  in  comparison  to 
mineral  acids.  In  conformity  with  ibis  view  the  readily  oxidizable  salts  con- 
tained in  organic  acids  would  be  particularly  adapted  to  the  prophylaxis  and 
therapy  of  the  disease.  Wright  tested  this  in  7  cases  of  scurvy  (for  the  most 
part  in  soldiers  during  the  siege  of  Ladysmith).  He  gave  appropriate  salts, 
particularly  sodium  lactate  (also  acetates,  carbonates  and  oxalates),  and  tested 
simultaneously  the  alkalinity  of  the  blood  by  a  method  which  lie  proposed,  now 
known  as  the  "  hemoalkalimetric."  In  all  of  these  cases  the  alkalinity  of  the 
blood  was  at  the  onset  very  low ;  and  by  this  treatment  an  increase  almost  or 
quite  to  the  normal  occurred  remarkably  soon  in  all  (with  the  exception  of  a 
fatal  case)  and  at  the  same  time  a  retardation  of  the  other  symptoms  of  the 
disease.  These  results  confirm  the  view  that  there  is  an  acid  intoxication  in 
scurvy. 

However  fascinating  the  potassium  theory  may  be,  it  is  by  no  means  abso- 
lutely proven,  and  it  does  not  contradict  the  view  that  scurvy  may,  in  spite  of 
this,  be  an  infectious  disease.  Scurvy  may  perhaps  be  assumed  to  be  an  infec- 
tions disease  of  a  non-contagious  nature  produced  by  a  microorganism  which 
funis  in  a  body  deficient  in  potassium  a  favorable  culture  medium  for  its 
development. 

PATHOLOGICAL  ANATOMY 

The  cadavers  are  characterized  usually  by  only  a  slight  degree  of  post 
mortem  rigidity,  and  by  the  appearance  of  numerous  livid  areas.  There  is 
also  a  tendency  to  rapid  cadaverous  alterations.  The  various  cutaneous  hem- 
orrhages present  during  life  remain  distinctly  visible  after  death.  The  lower 
extremities  are  frequently  edematous.  Upon  microscopic  investigation  of  the 
hemorrhagic  areas  we  note  that  in  the  smaller  (petechia')  the  point  of  exit 
of  the  Mood  i>  usually  the  capillary  network  in  the  area  Burrounding  the  hair 
follicle;  the  larger  hemorrhages  (suggillations  and  ecchymoses)  originate 
(piite  differently  from  superficial  or  deeper  layers  of  the  corium  according  to 
their  seal  and  their  extent.  The  erythrocytes  which  have  exuded  -how  all 
Btages  of  decolorization  and  of  decomposition.  The  surrounding  tissue  is  per- 
meated by  hemoglobin  of  various  colors. 

A-  tho  cause  of  the  hardenings  and  ecchymoses  in  the  subcutaneous  con- 
nective tissue  and  in  the  muscles,  various  infiltrations  of  blood  are  found, 
partly  diffuse,  in  part  sharply  demarcated,  and.  according  to  the  time  of  their 

appearance,   of   differenl    color-    and    consistence.      In    the   old    foci    where    the 

tissues  are  not  ye\  regenerated,  instead  of  the  fibrin  coagula  we  find  tough 
cicatricial  masses  of  connective  tissue  in  the  surroundings  of  which  the  mus- 
cular tissue  is  partly  rigid,  partly  atrophic,  and  the  tendon-  either  to  a  great 
extent  adherent  to  the  muscles  or  -o  hardened  that  movement  is  impossible. 
In  tin-  way  ankylosis  and  deformities  occur,  Buch  as  club-foot,  which  will  be 
discussed  later.  In  the  cavity  of  the  joint-  a  -eroii-  or  even  hemorrhagic  effu- 
sion i-  occasionally  found.     The  wall-  are  frequently  unchanged.     If.  how- 


400  THE  HEMORRHAGIC  DIATHESES 

ever,  hemorrhages  have  occurred,  more  or  less  extensive  ulcerations  of  the  cap- 
sule of  the  joint,  hemorrhagic  effusions  between  the  bones  and  the  cartilage, 
and  hemorrhagic  softening  of  the  epiphyses  are  noted.  Corresponding  to  the 
clinical  symptoms,  we  find  between  the  periosteum  and  bones  effusions  of  blood 
in  different  stages  of  coagulation  or  decomposition,  ulceration  of  the  periosteum, 
wasting  and  even  suppuration  of  the  cartilage  of  the  joint,  and  necrotic  changes 
in  the  bones.  Sometimes  the  insertions  of  the  muscles  are  loosened  by  these. 
In  the  interior  of  the  bone  also,  particularly  in  the  spongiosa,  hemorrhagic 
effusions  take  place. 

In  the  bone-marrow  lymphoid  transformation  has  not  infrequently  been 
observed. 

In  infantile  scurvy  an  epiphyseal  separation  is  occasionally  observed,  and 
in  about  45  per  cent,  of  the  cases  rickets  also  is  present. 

Very  important  changes  occur  in  the  digestive  tract.  The  mucous  mem- 
brane of  the  mouth,  except  that  of  the  gums,  is  but  slightly  altered;  now  and 
then  hemorrhagic  areas  and  erosions  are  noted.  The  gums  are  invariably 
swollen,  moderately  reddened,  and  completely  permeated  by  red  blood-corpus- 
cles. In  older  cases  there  is  a  coarse  thickening  as  the  result  of  proliferation 
of  the  connective  tissue.  Frequently  the  surface  is  ulcerated  or  necrotic. 
Babes  differentiates  microscopically  five  layers  in  a  sequence  from  without 
inward  which  he  describes  as  follows:  1.  The  upper  layer  for  the  most  part 
is  denuded  of  epithelium,  moderately  thick,  pale,  resembling  a  diphtheritic 
membrane,  and  permeated  with  but  few  nuclear  fragments  and  by  various 
bacteria,  particularly  streptococci;  2.  A  layer  about  0.1  mm.  in  thickness, 
without  structure ;  upon  staining  with  Loftier  blue  it  is  seen  as  a  film  of  bent, 
extraordinarily  fine  bacilli,  often  showing  long  wavy  forms  which  may  reach 
the  deeper  tissues  and  the  superficial  layer  in  the  form  of  sheaves  or  lines, 
and  in  the  latter  form  they  permit  the  recognition  of  granular  decomposition ; 
3.  Mononuclear  and  polynuclear  round  cells;  4.  Mucous  membrane  tissue  with 
edematous  swelling,  and  a  granular  exudate  with  numerous  bacilli  of  the 
variety  described  under  2.  In  the  walls  of  the  vessels  and  in  their  surround- 
ings swollen  spindle  cells  with  reticulated  protoplasm  which  may  be  well 
stained  by  methylene-blue ;  5.  Markedly  dilated  larger  vessels  with  large  spindle 
cells  in  their  walls. 

Upon  the  gastric  and  intestinal  mucous  membranes  infiltrations  of  blood 
are  frequently  found  ;  also  ulcerative  losses  of  substance,  besides  necrotic  and 
diphtheritic  changes.  In  those  cases  which  run  their  course  with  bloody  diar- 
rhea, special  pathological  processes  are  found  in  the  colon.  The  mucous  mem- 
brane is  swollen,  friable,  and  covered  with  a  hemorrhagic  mass  which  may  be 
readily  peeled  off.  The  tissue  lying  beneath  is  softened  or  completely  decom- 
posed. 

Cases  are  also  noted  in  which  the  follicles  show  pathological  changes,  and 
in  which  the  alterations  have  been  limited  to  these.  They  are  frequently  ulcer- 
ated, surrounded  by  dense  hemorrhagic  infiltration. 

In  the  large  glandular  organs  of  the  abdomen,  the  liver  and  the  pancreas, 
no  special  changes  are  found  except  hemorrhages  and  fatty  degeneration.  The 
spleen  is  usually  enlarged,  soft,  even  fluctuating,  and  occasionally  exhibits 


SCURVY  401 

infarcts  over  which  the  capsule  of  the  spleen  shows  the  remains  of  an  inflam- 
mation that  has  run  its  course  (circumserihed  perisplenitis).  The  kidneys 
rarely  reveal  pathologic  changes;  only  when  much  albumin  has  heen  excreted 
in  the  urine  a  more  or  less  advanced  parenchymatous  nephritis  may  he  noted, 
while  milder  grades  of  albuminuria  leave  no  trace. 

Amyloid  degeneration  of  the  kidneys  I  have  never  seen  in  scurvy,  and  this 
as  well  as  infarcts  appears  to  occur  very  rarely.  However,  hemorrhages  under 
the  capsule,  and  into  the  mucous  memhranes  of  the  urinary  passages,  are  not 
rarely  met  with. 

The  pleura?  and  the  pericardium  arc  very  frequently  covered  with  hemor- 
rhages. The  pleural  cavities  and  the  pericardium  occasionally  contain  very 
large  amounts  of  a  slightly  hemorrhagic  fluid  or  even  pure  hlood.  Fihrinous 
deposits  are  not  rare. 

The  heart  muscle  is  pale,  flaccid,  often  permeated  by  hemorrhages,  occa- 
sionally showing  fatty  degeneration.  The  valves  are  intact,  provided  an  acute 
endocarditis  has  not  complicated  the  course  of  the  disease;  it'  so,  the  signs 
of  an  acute  endocarditis  verrucosa  or  ulcerosa  may  he  met  with. 

In  the  lungs  there  is  usually  hemorrhagic  edema  and  hypostatic  congestion 
in  the  lower  Lobes  posteriorly;  occasionally,  as  severe  complications,  croupous 
pneumonia  or  hemorrhagic  infarcts,  hut  rarely  gangrene.  The  mucous  mem- 
brane of  the  respiratory  passages  is  often  covered  with  petechia;  and  with  a 
hemorrhagic   mucus;   there   is  edema   of   the   larynx. 

Besides  fatty  degeneration  and  occasionally  hemorrhagic  imbibition  of  the 
heart  muscle,  the  same  changes  are  found  in  the  muscles  of  the  body,  particu- 
larly those  of  the  hack,  thigh  and  arms. 

SYMPTOMATOLOGY 

The  disease  is  characterized  by  two  main  groups  of  symptoms:  1.  By  an 
intense  swelling  of  the  gums  combined  with  Loosening  and  hemorrhage,  to 
which  arc  often  added  ulceration  and  decomposition  with  extreme  fcetor  ex 
ore;  2.  By  numerous  extravasations  of  hlood  under  the  skin,  in  the  mucous 
membranes,  in  the  coats  of  the  eye.  in  the  muscles,  into  the  cavities  of  the 
body,  into  the  joints,  under  the  periosteum,  etc. ;  these  give  rise  t"  further  dis- 
turbances which  are  to  he  looked  upon  partly  as  mechanical,  as,  I'm-  example, 
the   pressure  of  the  intrapericardial   effusion  of  Mood   upon   the  heart.     In 

severe  cases  a  general  cachexia  of  the  mOSl  SerioUS  nature  is  added.  This 
cachexia    is   usually   the    first,  and    for  a    Ion-'  lime   the   only,  symptom   of   the 

disease,  and  as  a  rule  appears  gradually.  At  firs!  the  patient-  are  languid  and 
show  a  loss  of  energy,  without,  at  the  on-et.  being  unable  to  follow  their  usual 
occupations;  the  lassitude,  however,  increases  steadily,  even  Blighi  exertion 
becomes  difficult,  and  give-  rise  to  palpitation  and  dyspnea.  To  this  is  added 
as  a  very  important  and  almosl  constant  symptom  pain  in  the  limhs.  and  partic- 
ularly arthritic  pain-,  which  are  of  marked  rheumatic  character  and  may  occur 

in  all  the  joint-,  hut  which,  a-  a  rule,  are  generally  localized  to  the  hovei-  ex- 
tremities, and  are,  therefore,  not  infrequently  confounded  with  Schonlcin's 
peliosis  rheumatica.  Increasing  weakness  and  sensitiveness  upon  exertion,  and 
absolute  loss  of  appetite  are  combined  with  a  growing  sensation  of  chilliness, 


402  THE   HEMORRHAGIC   DIATHESES 

as  well  as  a  great  tendency  to  somnolence,  the  latter  symptom,  however,  being 
by  no  means  relieved  by  frequent  slumber. 

Corresponding  to  the  advancing  symptoms  of  the  disease,  the  external 
signs  of  the  affection  become  noticeable.  The  expression  of  the  face  denotes 
suffering,  the  lines  are  flaccid,  the  freshness  of  the  "complexion  gives  way  to  a 
cyanotic  pallor,  the  visible  mucous  membranes  are  of  a  livid  color,  the  eyes 
are  dull,  sunken  in  the  orbits  and  are  surrounded  by  rings.  The  skin  of  the 
body  loses  luster  and  smoothness,  it  becomes  dry  and  fissured,  and  occasionally 
desquamates  as  in  pityriasis  of  the  aged.  Upon  the  skin  brownish  spots  are 
observed,  similar  to  the  bronze  discoloration  in  Addison's  disease.  At  the 
onset  fever  is  usually  absent.  With  loss  in  strength  advancing  emaciation 
goes  hand  in  hand.  To  the  same  extent  the  pulse  loses  in  tension  and  volume 
and  is  slow,  but  becomes  for  the  time  full  and  frequent  whenever  the  patient 
makes  a  comparatively  slight  bodily  exertion.  The  subjective  sensation  of 
palpitation  of  the  heart  is  combined  with  this,  without,  however,  either  in 
rest  or  after  movement,  any  conspicuous  change  being  revealed  by  physical 
examination  of  the  heart. 

The  constitutional  phenomena  just  mentioned,  to  a  certain  extent  pro- 
dromes of  the  disease,  may  be  entirely  absent,  and  the  patient  be  attacked  sud- 
denly— without  a  prodromal  stage — with  the  characteristic  symptoms.  Usu- 
ally, however,  these  symptoms  precede  by  a  considerable  time,  the  period 
varying  between  several  days,  usually  from  eight  to  fourteen,  and,  in  excep- 
tional cases,  several  weeks. 

The  most  conspicuous  site  for  the  characteristic  symptoms  of  scurvy  is  the 
gums,  and  we  must  emphasize  that  only  those  areas  of  the  gums  are  attacked 
which  correspond  to  points  in  the  jaw  in  which  the  teeth  are  inserted;  so  that, 
for  example,  in  children  and  in  the  aged,  in  those  areas  in  which  no  teeth  have 
appeared,  or  in  those  from  which  they  have  already  fallen  out,  the  gums  show 
no  lesion.  Where,  however,  through  carious  processes  the  teeth  have  partially 
decayed,  or  where,  after  disappearance  of  the  crown  the  alveoli  still  possess 
roots,  the  disease  preferably  localizes  itself.  The  anterior  gums  usually,  and 
especially  at  the  onset  of  the  disease,  are  decidedly  implicated,  but  not  the  rest 
of  the  mucous  membrane  of  the  mouth.  At  first  the  free  border  of  the  gums, 
particularly  the  bit  which  projects  in  the  intermediate  space  between  two  teeth, 
begins  to  swell,  rising  above  its  surroundings,  at  the  same  time  assuming  a 
deep  bluish-red  color.  This  color  is  not  only  the  expression  of  an  edematoiis 
hyperemia  but  usually  of  a  hemorrhagic  infiltration  as  well,  whereby  it  differs 
distinctly  from  other  forms  of  stomatitis. 

The  affection  of  the  gums  rapidly  advances,  the  swollen  areas  are  fre- 
quently extremely  painful,  and  a  very  characteristic  symptom  appears;  mod- 
erate pressure,  a  mere  touch,  causes  profuse  hemorrhage.  The  longer  the 
duration  of  the  disease,  and  the  more  severe  its  form,  the  more  extensive  the 
affection  of  the  gums.  At  the  same  time,  the  swelling  becomes  greater  and 
greater,  so  that  frequently  nothing  of  the  teeth  can  be  seen. 

Simultaneously  an  intensely  disagreeable  odor  of  decomposition  proceeds 
from  the  mouth,  and  in  the  later  course  of  the  disease  becomes  quite  unbear- 
able.    The  inflammatory  swelling  increases  still  further,  deposits  of  a  dirty, 


SCURVY  403 

grayish  white  color  resembling  those  of  diphtheria  form,  adhering  closely 
to  the  mucous  membrane,  and  after  their  removal  the  mucous  memhrane  suf- 
fers a  more  or  less  decided  loss  in  substance,  and  a  bleeding,  very  painful  sur- 
face remains.  Sometimes  the  mucous  memhrane  even  becomes  gangrenous. 
The  surface  is  coated  with  a  dirty,  fetid  deposit,  the  upper  layers  of  which 
slough  off,  and  are  expectorated  with  the  saliva.  If  this  state  continue  for 
a  long  time  the  gums  may  become  gangrenous  and  necrose,  the  alveoli  may 
he  exposed  to  a  great  extent,  and  the  teeth  may  become  loose  and  fall  out. 
The  unfortunate  patient  now  sutler-  tortures,  for  these  symptoms  increase 
in  severity  and  usually  many  others  go  hand  in  hand,  and  particularly  the 
extremely  severe  cachexia.  The  latter  is  probably  not  a  consequence  of  the 
various  severe  local  symptoms.  On  the  contrary,  it  ushers  in  the  affection, 
forms  a  principal  factor  in  all  the  phases  of  the  disease,  and  is  the  primal 
cause  of  the  intensity  of  the  individual  symptoms. 

In  many  patients,  and  according  to  the  severity  of  the  disease  of  the 
gums,  there  is  an  increase  in  the  secretion  of  saliva,  probably  due  to  reflex 
causes,  so  that  a  hemorrhagic  fetid  fluid,  in  which  infusoria  and  low  fungi 
may  he  recognized,  streams  almost  continuously  from  the  mouth. 

If  the  affection  terminate  in  recovery,  complete  restitution  may  occur, 
and  the  teeth  which  were  previously  loose  may  again  become  firmly  rooted. 
Mori'  frequently  a  tough  tissue  resembling  cicatrix  forms  and  remains  for  life. 

Mechanical  effects  produced  by  chewing  and  mechanical  irritation  have 
been  assumed  to  he  the  cause  of  the  almost  invariable  inflammation  of  the  gums 
in  scurvy;  to  these  may  he  added  the  inherent  tendency  of  the  disease  to 
inflammation. 

In  children,  besides  the  usual  form  of  simple  stomatitis,  another  variety 
designated  as  aphthous  stomatitis,  an  inflammatory  affection  of  the  mucous 
membrane  of  the  mouth,  sometimes  occurs,  particularly  during  the  period  of 
dentition,  i.e.,  between  the  ninth  month  and  the  middle  of  the  third  year. 
Henoch  says  regarding  this:  In  some  of  the  cases  a  disagreeable  odor  from  the 
month  i-  added  to  the  symptoms  described,  and  minute  investigation  always 
reveals  a  hyperemic  gum  which  bleeds  readily,  which  may  even  -how  a  Lrravi<h 
yellow  detritus  of  friable  character  that  may  he  readily  loosened  with  a  spat- 
ula. Thi-  form  of  stomatitis,  which  is  of  a  decidedly  contagious  nature. 
usually  runs  a  favorable  course;  more  rare  is  another  which  i-  designated  by 
the  name  of  ulcerative  stomatitis.  While  the  fibrinous  plaques  which  are 
invariably  presenl  in  the  latter  affection  are  absenl  in  the  former,  the  impli- 
cation of  the  gums  requires  the  careful  attention  of  the  physician.  These  are 
dark  red  or  bluish  red  ami  swollen,  they  bleed  readily  ami  decompose  from  the 
edge  surrounding  the  tooth,  gradually  forming  a  grayish  yellow  paste;  the 
crown  of  the  tooth  i-  exposed,  and  finally  becomes  loosened.  Upon  pressure  a 
purulent  fluid  exudes  from  the  -pace  between  the  loosened  gums  and  the  teeth. 

a    fetid    odor   conn-    from    the    mouth,    and    the    BUlTOUnding   soft    parts.      The 

cheeks  and  the  submaxillary  connective  tissue  frequently  -how  edematous 
swelling.  Occasionally  the  process  attacks  the  periosteum  of  the  jaw.  extend- 
ing down  into  the  alveolar  pro<  rasing  the  teeth  to  fall  out.  and  finally 
gives  rise  to  partial  oecrosia  of  the  jaw. 


404  THE  HEMORRHAGIC  DIATHESES 

This  description,  after  Henoch,  corresponds  to  analogous  processes  in 
scurvy  with  the  exception  of  the  necrosis  of  the  jaw,  and  this  probably  occurs 
very  rarely  in  scurvy.  Henoch,  one  of  our  greatest  pediatric  clinicians,  in  his 
description  of  stomatitis  fails  to  mention  scurvy,  and  assigns  no  place  to  this 
disease  in  his  lectures  upon  diseases  of  children ;  I  conclude  from  this  fact 
that  he  is  of  the  opinion  that  the  stomatitis  of  infancy  has  nothing  in  common 
with  scurvy  and,  moreover,  that  he  has  not  observed  scurvy  in  nurslings  or  in 
the  years  of  infancy.1 

That  there  is,  however,  such  a  condition  as  infantile  scurvy  may  be  seen 
from  the  American  Collective  Report,  in  which  it  is  stated  that  among  372 
cases  which  occurred  during  infancy,  particularly  during  the  period  between 
the  seventh  and  fourteenth  months,  in  only  16  cases  were  the  gums  unaffected; 
in  the  remaining  313  cases  there  is  mention  of  either  swelling  and  loosening 
of  the  gums  or  of  ulcerative  processes  in  the  gums.  Certainly,  Henoch's  cases 
were  not  scurvy,  for  he  reports  in  them  no  extravasations  of  blood  into  the 
skin  or  the  mucous  membranes;  neither  can  we  doubt  that  cases  of  ulcerative 
stomatitis  which  are  not  of  a  scorbutic  nature  may  occur  also  in  adults. 

In  view  of  the  entirely  different  etiology  of  stomatitis  and  scurvy  we  must 
clearly  separate  the  oral  affections  of  the  two  diseases,  and  we  shall  only  refer 
to  scurvy  if,  besides  the  stomatitis,  other  symptoms,  to  be  more  minutely  de- 
scribed later,  are  also  present.  Among  these  are  hemorrhages  into  the  skin, 
into  the  subcutaneous  connective  tissue,  in  the  mucous  and  serous  membranes, 
into  the  joints,  muscles,  etc. 

The  hemorrhages  into  the  skin  usually  occur  in  the  form  of  petechia?  which 
vary  greatly  in  size.  They  occur  early  and  most  profusely  upon  the  lower  leg, 
particularly  upon  the  extensor  surfaces;  the  trunk  and  the  other  extrem- 
ities are  often  affected  later,  the  face  invariably  remaining  entirely  exempt. 
If  they  appear  in  great  numbers  the  impression  is  given  that  a  paint  brush 
has  been  dipped  in  blood  and  spattered  over  these  areas.  Traumatic  influ- 
ences, a  blow,  pressure,  especially  such  as  is  caused  by  the  wearing  of  tight 
clothing  (garters,  girdles,- belts,  etc.),  not  infrequently  produce  these  hemor- 
rhages and  give  to  them  a  definite,  under  some  circumstances  a  characteristic, 
form  and  shape;  for  example,  the  form  of  streaks  (vibices).  Often  an  ex- 
tremity is  profusely  covered  with  them,  and,  according  to  their  age,  they  pre- 
sent a  dark  red,  brownish  red,  green  or  yellowish  color,  corresponding  to  the 
well-known  changes  in  color  which  extravasated  blood  or  hemoglobin  presents 
when  undergoing  alteration.  These  hemorrhages  have  a  special  predilection 
for  the  gluteal  region,  where  they  occasionally  develop  extensively. 

The  first  effusions  into  the  skin  frequently  form  around  a  hair  follicle,  so 

i  In  the  latest  edition  of  Henoch's  book,  in  the  description  of  Barlow's  disease,  there 
is  mention  of  a  change  in  the  gums,  as  follows :  "  To  these  symptoms  almost  invariably 
is  added  a  spongy  swelling  of  the  gums  with  fetor  and  tendency  to  hemorrhages  as  in 
the  case  of  scurvy,  and  this  is  most  marked  in  the  cases  where  teeth  are  already  present." 
Then  follows  another  statement  of  importance :  "  For  the  present  we  may  only  assume 
that  we  are  here  dealing  (in  Barlow's  disease)  with  a  form  of  the  hemorrhagic  diathesis 
that  has  much  in  common  with  scurvy  but  does  not  appear  to  be  identical  with  it." 
A  special  description  of  scurvy  is,  however,  not  found  in  his  latest  edition. 


SCURVY  405 

that  apparently  the  capillary  vessels  of  the  latter  may  be  looked  upon  as  the 
starting  point  of  the  hemorrhage.  The  effusions  of  blood  appear  as  though 
punctured  by  the  little  hairs  in  this  area.  The  hair  then  becomes  dry,  fibril- 
lates,  and  falls  out.  The  region  about  the  nails  is  also  frequently  the  seat  of 
hemorrhages;  when  these  suppurate,  the  process  often  extends  to  the  bed  of 
the  nail  so  that  it  leads  to  paronychia,  that  is.  an  onychia  scorbutica,  as  the 
result  of  which  the  nail  dies.  The  ulcers  upon  other  parts,  particularly  upon 
the  lower  extremities  and  the  buttocks,  may  be  of  extraordinary  size.  Some 
are  covered  with  dark,  firm  crusts,  some  have  a  dirty  base  which  is  covered 
with  decomposed  purohemorrhagic  shreds  of  tissue,  or  flat  granulations  may 
be  seen  which  bleed  at  the  slightest  touch.  Usually  the  ulcers  secrete  continu- 
ously a  thin  hemorrhagico-purulent.  sometimes  even  ichorous,  fluid  which  has 
a  most  offensive  odor.  Unless  cicatrization  of  the  ulcers  occurs  previous  to 
general  improvement  (and  this  is  rare)  these  frequently  spread  to  the  sur- 
rounding tissues,  or  even  invade  them  deeply,  thus  causing  the  erosion  of 
larger  vessels  and  hemorrhages  which  may  terminate  fatally.  But  even  with- 
out tins  serious  outcome  these  cutaneous  ulcers  are  of  bad  prognosis,  for  their 
profuse  secretion  greatly  debilitates  the  organism. 

The  hemorrhages  into  the  subcutaneous  connective  tissue  and  into  the 
muscles  may  be  widely  distributed,  and  attain  the  size  of  a  plate  or  even  be 
larger.  Sometimes  they  develop  acutely,  sometime-  slowly;  in  the  former 
case  they  are  usually  accompanied  by  pain  and  an  increase  in  temperature. 
The  skin  above  them,  as  a  rule,  can  be  but  slightly  moved  or  not  at  all,  it 
ha-  a  doughy  sensation,  is  painful  upon  pressure  and  feels  hot.  In  the  case 
of  these  subcutaneous  hemorrhages  the  lower  extremities  are  the  chief  -eat, 
as  they  are  of  petechias,  particularly  the  region  of  the  tendo  Achillis  and  the 
popliteal  space.  At  the  onset  there  is  noticed  a  soft  -welling  which  later 
becomes  harder,  and  is  finally  as  hard  as  wood.  The  margins  of  the  tumor 
are  not  always  sharply  defined.  The  skin  above  the  swelling  is  not  movable 
and  the  swelling  is  of  ten  not  sharply  marked  off  from  the  surrounding  tissues. 
Over  the  swelling  the  skin  -hows  decided  redness  and  edema:  it  is  shiny,  hot 
and  painful.  After  a  few  days  these  Bymptoms  ameliorate,  and  the  redness 
turns  to  a  dull  brown.  Then  absorption  occurs,  the  -kin  desquamates,  and 
always  retain-  a  dark  pigmentation.  Bui  the  swelling  may  Boften  and  even- 
tually  rupture,  and   a  quantity  of  necrosed   gangrenous   tissue   mixed    with 

blood   sloughs  away.      The  result   is  a  deep   ulcer.      The  COUTSe  is.  however,  not 

always  so  acute.  The  swelling  and  hardening  may  occur  much  more  grad- 
ually; pain  and  fever  may  he  absent.  Upon  the  -kin  there  may  appear  tin1 
sLms  of  a  more  or  less  well-developed  suggillation,  according  to  whether 
the  process  runs  it-  course  auperficially  or  in  the  deeper  tissue.  A.s  a  matter 
of  course  such  foci  decidedly  limit  the  function  of  the  muscles,  whether  they 
are  located  in  the  muscles  themselves  or  in  the  neighboring  connective  tissue. 

Whet)    di-ea-e    of    the    lllll-cle    is    combined    \\i|||    ,|i-ea-e    of    the   connective    ti--lie. 

it  is  often  iinpo--ilile  for  the  physician  to  make  a  differential  diagnosis.  In 
the  niii-cle-  quite  isolated  foci  may  he  found  which  are  characteristic  in  that 
the  integumenl  ovct  them  scarcely  -how-  change.  These  foci  vary  greatly  in 
the  symptom-  which   they   produce;  some  are  circumscribed,  Borne  diffuse, 


406  THE  HEMORRHAGIC  DIATHESES 

some  painful,  some  painless,  some  acute  and  accompanied  by  fever,  some  grad- 
ual in  onset  and  afebrile  in  course. 

Hemorrhages  from  the  mucous  membranes  are  decidedly  less  frequent, 
but  they  may  cause  death  or  hasten  death  by  inanition.  We  must  mention 
hemorrhages  from  the  nose,  hematemesis,  enterorrhagia,  hematuria,  metror- 
rhagia and  hemoptysis.  For  a  long  time,  severe  epistaxis  has  been  greatly 
dreaded;  it  is,  however,  not  very  frequent,  but  can  rarely  be  stopped  without 
packing,  and  sometimes  causes  death.  These  hemorrhages  rarely  occur  spon- 
taneously, but  are  usually  the  result  of  slight  injuries  to  the  nasal  mucous 
membrane;  they  may  follow  strenuous  blowing  of  the  nose.  The  fact  that  an 
external  cause  is  usually  required  to  produce  the  hemorrhages  which  are  so 
characteristic  of  scurvy,  Immermann  believes  will  explain  the  circumstance 
that  the  gums  are  usually  the  seat  of  these  symptoms.  He  is  of  the  opinion 
that  the  stomatitis  marginalis  of  scurvy  is  also  secondary,  inasmuch  as  the 
gums,  considering  the  delicacy  of  their  histologic  structure,  are  so  frequently 
and  decidedly  exposed  to  mechanical,  chemical  and  thermic  irritations — par- 
ticularly as  the  development  of  the  affection  of  the  gums  is  always  appar- 
ently associated  with  the  presence  of  teeth  in  the  jaw,  and  therefore  with  the 
process  of  chewing.  It  may  also  be  here  emphasized  that  the  gums  are  not 
exclusively  the  seat  of  the  disease,  nor  are  they  the  first  typical  points,  but 
severe  cases  may  run  their  course  without  an  implication  of  the  gums,  and  in 
general  the  sequence  of  the  individual  symptoms  and  the  number  of  the  impli- 
cated organs  may  be  very  variable. 

Hemorrhage  from  the  mucous  membranes  of  the  stomach  and  intestines  is 
decidedly  more  rare  than  from  the  mucous  membrane  of  the  nose,  and  is  prone 
to  occur  when  the  bowel  is  stimulated  to  decided  peristalsis;  as,  for  example, 
after  the  administration  of  purgatives.  Its  development  may,  therefore,  be 
compared  with  epistaxis  after  violent  blowing  of  the  nose.  In  rare  cases  dys- 
entery is  simultaneously  present.  Hemoptysis  occurs  only  occasionally  owing 
to  a  coexisting  tuberculosis  or  a  fibrinous  pneumonia,  the  latter  disease  then 
having  its  starting  point  in  a  hemorrhagic  pulmonary  infarct. 

Besides  these  hemorrhages  which  appear  upon  the  surface,  or  from  organs 
with  an  external  outlet,  others  may  occur  in  the  internal  cavities,  or  there 
may  be  bleeding  even  into  the  organs  themselves.  These  represent  a  severe 
form  of  the  disease ;  they  cause  extreme  debility  or  may  even  be  the  immediate 
cause  of  death.  Among  these  we  must  mention  first  the  pleural  and  peri- 
cardial hemorrhages  some  of  which  may  be  looked  upon  as  forms  of  non- 
inflammatory hemothorax  which  occasionally  leads  to  an  inflammation  of  the 
serosa,  some  as  inflammatory  hemorrhagic  effusions  which,  by  compression  of 
the  lungs  or  paralysis  of  the  heart,  decidedly  increase  the  danger  to  life. 
That  these  effusions  into  the  serous  cavities  (which  may  also  occur  in  the 
peritoneum)  are  susceptible  of  absorption  is  unquestionable. 

Meningeal  hemorrhages  have  also  been  observed,  and  may  be  diagnosticated 
by  pain,  paresthesia,  spasms,  contractures,  paralyses,  and  apoplectiform  attacks. 
In  some  cases  death  occurs  with  the  symptoms  of  apoplexy,  but  actual  cases 
of  true  cerebral  hemorrhage  appear  to  be  extraordinarily  rare.  More  frequent 
are  scorbutic  changes  in  the  eye.     Hemorrhages  and  inflammation  of  the  con- 


SCURVY  407 

junctiva,  hemorrhages  into  the  anterior  chamber  of  the  eye,  or  choroiditis 
hemorrhagica  have  been  noted.  The  subconjunctival  hemorrhages  may  cause 
loosening  of  the  conjunctiva,  and  to  such  an  extent  that  the  membrane  swells 
out  under  the  eyelid,  frequently  covering  the  eye-ball  to  a  great  extent.  Occa- 
sionally iritis  also  occurs.  All  of  these  symptoms  may  improve  or  may  lead 
to  corresponding  permanent  changes.  In  very  severe  cases,  bilateral  pan- 
ophthalmitis usually  occurs  and  leads  to  entire  loss  of  sight.  These  cases 
invariably  terminate  fatally.  Seggel  observed  in  a  mild  case  hemorrhages  into 
the  vascular  wall  of  the  retinal  vessels,  besides  frequent  repetitions  of  sub- 
conjunctival hemorrhages,  and  a  swelling  due  to  hemorrhage  into  the  pia 
sheath  of  the  optic  nerve  with  a  slight  cloudiness  of  the  papilla.  Not  infre- 
quently in  the  course  of  the  disease,  as  prodrome,  or  as  sequel,  hemeralopia 
or  night-blindness  is  observed — a  condition  in  which  the  sense  of  right  is  more 
or  less  lost  during  dusk  and  at  night.  Nothing  is  known  of  the  causal  rela- 
tion of  the  underlying  affection  to  these  phenomena. 

A  particular  and  important  group  of  symptoms  is  that  affecting  the  tissues 
constituting  the  joints,  including  the  cartilage  and  the  bone.  Besides  the 
more  or  less  widely  distributed  rheumatoid  pains  in  the  joints,  painful  swell- 
ings of  the  latter,  due  to  effusions,  are  observed.  These  latter  may  be  purely  ser- 
ous, but  more  frequently  consist  of  a  sanguinolent  fluid.  Sometimes  there  is 
also  suppuration  of  the  joint  with  subsequent  erosion  and  deformity,  and  finally 
true  ankylosis.  Inasmuch,  however,  as  the  affection  usually  terminates  in  re- 
covery, these  effusions  are  generally  absorbed  without  ankylosis  developing.  In 
the  bones,  particularly  after  mechanical  injuries  not  necessarily  at  all  severe, 
hemorrhages  occur,  or  inflammatory  periosteal  effusions  between  the  periosteum 
and  the  bone  arise.  Indurated  and  very  painful  swellings  result,  which,  how- 
ever, may  slowly  subside,  or  may  lead  to  local  necrosis  and  the  formation  of 
Bequestra.  At  the  epiphyses  the  coverings  of  the  cartilage  become  detached. 
The  long  tubular  bones  of  the  lower  extremities  are  chiefly  attacked,  next  those 
of  the  upper  extremity,  frequently  also  the  ribs,  in  which  case  the  process  Leads 
to  detachmenl  from  the  Bternum.  The  kind  of  aid  given  by  scurvy  to  many 
intercurrent  affections  may  be  suspected  if  we  notice  how  in  fresh  cicatrices, 
or  in  those  previously  formed,  it  produces  a  Boftening  of  the  callus. 

During  the  progress  of  the  symptoms  described  the  constitutional  condi- 
tion of  the  patient  deteriorates.  Ee  becomes  cachectic  looking,  the  fat  and 
the  musculature  gradually  disappear.  Fever  may  be  absent,  in  other  cases 
may  be  slight,  without  conforming  to  any  definite  type.  Decided  rises  in 
temperature  are  generally  due  to  complications  or  to  suppuration.  Sometimes 
Bwelling  of  the  spleen  is  noted  ;  this,  however,  can  by  no  mean-  be  looked  upon 

a-    specific.      The   Bymptoms   on    the   part    of   the  heart    correspond    with    those 

of  other  anemic  conditions — systolic  murmurs  and  dilatation.  Clinically  the 
most  prominent  Bymptoms  are  cardiac  palpitation  and  dyspnea  upon  compara- 
tively slight  movement  and  exertion.  The  small,  frequent,  and  slightly  irreg- 
ular pulse  is  notable.  In  the  course  of  the  disease  endocarditis  occasionally 
occurs,  hut  clinically,  in  the  majority  of  the  cases.  ,an  scarcely  be  recognized, 
being  anatomically  characterized  by  a  delicate  circle  of  excrescences  upon  the 
free  border  of  the  mitral  valve  or  the  aortic  valve.     Inder  some  circumstances 


408  THE   HEMORRHAGIC  DIATHESES 

it  runs  its  course  with  the  symptoms  of  ulcerative  endocarditis.  It  is  to  be 
hoped  that  we  may  succeed  in  discovering  in  the  endocardial  deposits  the 
pathogenic  agent  of  the  disease,  which  so  far  has  been  unsuccessfully  looked 
for  in  the  blood.  On  the  part  of  the  digestive  tract  we  have  occasional  diar- 
rhea which  may  be  of  a  dysenteric  character.  Several  times  the  combination 
of  scurvy  with  true  dysentery  has  been  observed.  Kidney  troubles  are  com- 
paratively slight ;  occasionally  transitory  albuminuria  is  met  with,  without  our 
being  able  to  conclude  from  this  the  presence  of  genuine  nephritis,  which  is  a 
rare  complication.  Reports  of  marked  hematuria  are  rare.  The  urine  is  fre- 
quently of  a  dark  color,  which  Kretschy  ascribes  to  an  increase  of  the  normal 
coloring  material  due  to  a  greater  destruction  of  red  blood-corpuscles.  In  se- 
vere cases  the  quantity  of  the  urine, especially  during  the  progress  of  the  disease, 
is  greatly  diminished;  peptonuria  occurs  as  well  as  albuminuria.  According 
to  v.  Jaksch  the  peptone  does  not  originate  in  the  blood  itself,  but  from  the 
hemorrhages  of  the  skin,  of  the  subcutaneous  cellular  tissue,  etc.  To  this  he 
ascribes  the  origin  of  the  profuse  urobilin. 

Of  course,  special  importance  has  been  attached  to  the  amount  of  potash 
in  the  urine,  but  the  reports  regarding  the  quantity  found  are  very  contra- 
dictory. Phosphoric  acid  is  said  to  be  increased ;  unquestionably  the  amount 
of  uric  acid  is  great,  especially  at  the  height  of  the  disease,  but  it  rapidly 
decreases  with  beginning  convalescence. 

In  the  blood,  apart  from  Klebs'  questionable  nomads,  nothing  character- 
istic has  been  found.  The  findings  correspond  in  the  main  with  those  of  severe 
anemia.  The  amount  of  hemoglobin  is  decreased,  and  in  severe  cases  not  only 
the  number  of  erythrocytes  but  also  their  hemoglobin  contents ;  poikilocytes 
and  microcytes  I  myself  have  frequently  found,  some  with  basophilic  granula- 
tions. Particularly  common  is  the  form  of  achromia  cell  described  by  me 
resembling  a  pessary.  Penzoldt  also  reports  the  presence  in  the  blood  of 
granular,  and  some  markedly  refractive,  bodies  which  he  looks  upon  as  embry- 
onic forms  of  red  corpuscles.  Macrocytes  also  are  said  to  have  been  found 
in  large  numbers.  According  to  the  reports  of  Laboulbene  the  number  of 
leukocytes  is  increased ;  this  I  am  unable  to  confirm  from  my  own  observations. 
The  reports  are  contradictory  regarding  the  amount  of  iron  in  the  blood. 
According  to  Opitz  and  Schneider  it  is  somewhat  increased;  according  to 
Duchek  it  is  nearly  normal,  and  according  to  Becquerel,  Kodier  and  Chalvet 
it  is  decidedly  decreased.  The  latter  has  also  determined  a  decrease  in  the 
amount  of  potassium. 

As  a  result  of  our  review  of  the  great  number  of  accounts  of  severe  symptoms 
in  past  epidemics  we  must  emphasize  our  impression  that,  at  least  in  Germany, 
the  severe  forms  of  the  disease  are  now  only  very  rarely  observed. 

Frequently  the  symptoms  are  limited  to  great  lassitude,  pain  in  the  joints 
and  limbs,  extensive  hemorrhages  into  the  skin  and  elsewhere,  and  more  or 
less  decided  hemorrhagic  inflammation  of  the  gums.  In  these  cases  the  entire 
course  is  comparatively  short. 

Scurvy  may  terminate  in  death  or  in  complete  or  partial  recovery.  Gen- 
erally recovery  is  exceedingly  slow,  and  weeks  and  months  pass  before  the 
different  processes  have  run  their  course.     The  disease  of  the  gums,  if  great 


SCURVY  409 

loss  of  substance  has  not  occurred,  steadily  improves,  the  swelling  disappears, 
and  restitutio  ad  integrum  takes  place.  On  the  other  hand,  permanent  changes 
in  the  form  of  cicatricial  retractions  or  hyperplastic  thickening  of  the  tissue 
may  remain,  which,  however,  do  not  give  rise  to  any  difficulties.  Of  the 
processes  in  the  skin,  the  small  hemorrhages  improve  most  readily.  They  go 
through  all  the  changes  that  hemoglobin  shows,  and  finally  disappear.  With 
an  improvement  in  the  general  condition,  the  cutaneous  ulcers  also  pursue  a 
favorable  course.  Their  surfaces  become  clean,  and  finally  skin  is  formed 
in  which  a  dark  pigmentation  remains  for  a  long  time.  The  swelling  in  the 
muscles  and  connective  tissue  also  gradually  recedes,  although  very  slowly,  so 
that  a  callus  is  often  evident  long  after  complete  recovery.  Not  rarely,  too, 
connective  tissue  proliferation  occurs  (as  in  the  gums),  the  result  of  which  is 
permanent  contraction  or  fixation  of  the  muscles  and  joints,  with,  for  example, 
the  formation  of  club-foot. 

DIAGNOSIS 

In  view  of  the  marked  symptoms,  the  conspicuous  epidemic  character  of  the 
disease,  and  the  extraordinary  circumstances  under  which  it  usually  arises,  the 
diagnosis  of  scurvy  can  scarcely  be  difficult. 

Difficulty  arises  only  when  we  are  dealing  with  sporadic  cases,  and  even  in 
these  a  careful  history  of  the  previous  conditions  of  the  life  and  residence  of  the 
patient  will  lead  to  a  recognition  of  the  affection.  If  we  remember  that  the 
greatest  number  of  epidemics  occur  upon  ships,  in  fortresses,  among  isolated 
bodies  of  troops,  ot  in  penal  and  eleemosynary  institutions,  thai  quite  definite 
etiologic  factors  snch  as  insanitary  conditions  of  life,  and,  above  all.  improper 
food  have  preceded  the  outbreak,  no  further  proof  is  needed  for  us  at  once  to 
recognize  the  disease.  The  disease  may  break  out  in  so  many  place-  that  it  is 
only  very  rarely  that  symptoms  are  at  all  -canty  in  a  given  case;  almost  always 
a  number  of  the  usual  symptoms  appear  simultaneously.  Serious  diagnostic 
difficulties  will,  therefore,  only  occur  in  isolated  cases  of  unusually  mild  char- 
acter. But  these  are  ju-t  the  ones  which  to-day  present  themselves  for  pro- 
fessional treatment. 

I'n-t    among   the  external    symptoms   we   have   learned    to   recognize   those 

which  almo-t  always  precede  the  local  phenomena  of  the  disease  and  increase 
with  it-  advance;  i.e..  the  general  cachexia.  Next  come  the  various  effusions 
of  blood  into  the  skin,  into  the  deeply  lying  connective  tissue  and  the  muscles, 
the  rheumatoid  arthritic  pain-  occasionally  present,  and.  above  all.  the  affec- 
tion of  the  gums.  The  niimher  of  di-ea-e-  which  may  lie  confounded  with  it 
is  verv  small.  First,  those  di-ea-e-  which  form  a  common  group  with  scurvy 
(hemophilia   and    morbus   maculosus   Werlhofii ).      Neither  i-  epidemic   in   any 

sense;  and  as  both  are  to  be  described  later  they  □ 1  uot  now  be  considered. 

I  will  -tale  here,  however,  that,  in  spite  of  the  external  similarity  of  many 
cardinal  Bymptoms,  the  di-ea-e  of  the  gums  i-  the  predominant    feature  in 

BCUrvy,  and    i-   not    present    in  either  of  the  other  di-ea-e-  mentioned. 

Cutan i-  hemorrhages,  especially  petechia?  and  -mall  ecchymoses,  are  met 

with  in  a  number  of  cachectic  di-ea-e-.  When  associated  with  rheumatoid  or 
arthritic  pain-  a  confusion  of  scurvy  with  peliosis  rheumatics  may  occur.     If. 


410  THE   HEMORRHAGIC  DIATHESES 

in  such  cases,  the  diagnosis  is  difficult,  it  must  be  remembered  that  scorbutic 
hemorrhages  are  generally  of  an  inflammatory  character,  while  in  the  other 
diseases  this  is  by  no  means  the  case.  Finally,  it  must  be  borne  in  mind  that 
in  scurvy  we  have  excellent  therapeutic  measures  under  the  action  of  which 
the  symptoms  usually  disappear  rapidly,  while  in  the  majority  of  the  other 
diseases  therapy  is  for  the  most  part  of  no  avail. 

PROGNOSIS 

While  the  prognosis  during  past  historic  epochs  was  usually  very  grave, 
to-day,  fortunately,  it  is  very  favorable,  especially  in  cases  other  than  the  most 
severe.  Naturally,  we  must  be  cautious  in  prognosis,  for  even  in  mild  and 
moderately  severe  cases  intercurrent  affections  may  bring  about  death.  The 
earlier  the  therapy  is  begun  the  inore  favorable  the  ultimate  result  and  the 
shorter  the  course,  although  even  under  favorable  circumstances  it  always 
requires  considerable  time  for  the  patient  completely  to  regain  his  strength. 
Complete  recovery  is,  of  course,  only  to  be  expected  in  those  cases  in  which  the 
disease  has  shown  itself  to  be  mild ;  in  other  cases  recovery  is  usually  incom- 
plete. Only  in  cases  in  which  no  loss  of  substance  has  occurred  can  a  complete 
restitutio  ad  integrum  be  expected. 

In  cases  which  terminate  fatally,  the  patient  usually  suffers  for  a  long 
time,  and  passes  through  many  complications  before  he  finally  succumbs  to 
general  exhaustion.  Yet  many  circumstances  may  lead  to  an  early  death. 
Among  these  by  far  the  commonest  are  hemorrhages  of  lethal  extent.  These 
may  be  from  the  gums,  from  the  nasal  mucous  membrane,  from  cutaneous 
ulcers,  eroded  arteries,  or  from  the  digestive  tract. 

More  frequently  death  results  from  complications,  particularly  dysentery 
and  croupous  pneumonia,  more  rarely  malignant  endocarditis,  the  cause  of 
which  is  to  be  sought  for  in  the  entrance  of  infectious  germs  from  the  ulcers. 
Quite  often  excessive  effusions  into  the  pleural  cavity  or  into  the  pericardium 
threaten  life;  sometimes  extreme  cardiac  asthenia  leads  to  a  fatal  result,  and 
if  the  patient  makes  an  unusual  exertion  or  rises  suddenly,  he  collapses  life- 
less, as  occasionally  happens  in  children  who  have  had  an  attack  of  diphtheria. 

PROPHYLAXIS  AND  TREATMENT 

Garrod's  teaching  that  a  deficiency  in  acid  vegetable  potassium  is  the  chief 
cause  of  the  disease  indicates  the  direction  in  which  a  prophylaxis  in  scurvy 
is  to  be  attained.  The  theory  of  Garrod,  although  correct  in  its  fundamental 
principles,  does  not  appear  to  be  absolutely  well-founded  throughout,  for  cases 
of  scurvy  develop  where  there  is  no  deficiency  of  potassium  in  the  food.  In 
the  epidemic  in  Rastatt  (1851-1852),  for  example,  there  was  no  deficiency  in 
fresh  vegetables;  nor  in  that  of  Ingolstadt  where,  in  spite  of  good  food,  such 
as  meat  and  potatoes,  an  epidemic  occurred  among  the  prisoners  of  war.  It 
has  therefore  been  assumed  that  it  is  not  the  deficient  administration  of  potas- 
sium, but  the  insufficient  retention  of  potassium  in  the  organism,  which  causes 
the  disease.  Unquestionably,  among  other  conditions,  the  increased  consump- 
tion of  potassium  in  the  body  plays  an  important  role.     If  the  theory  of  Bunge 


SCURVY  411 

is  correct,  the  excessive  ingestion  of  talile  salt  produces  an  increased  excretion 
of  potassium.  Thus  the  fact  can  easily  be  accounted  for  that  the  continued 
use  of  salted  meat  frequently  causes  scurvy,  although  this  is  denied  by  many. 

In  consonance  with  opinions  generally  held,  plentiful  amounts  of  acid 
vegetable  potassium  should  be  administered  to  the  organism  in  the  form  of 
fresh  green  vegetables  such  as  new  potatoes,  spoonwort  (scurvy  grass),  cabbage, 
spinach,  water  cress,  radishes,  sorrel,  sauerkraut,  carrots,  turnips,  onions,  arti- 
chokes, asparagus  and  lettuce,  also  juicy  fruits,  oranges,  milk,  fresh  meat,  meat 
extract,  meat  juice,  particularly  puro  (from  the  laboratory  of  Scholl  in 
Munich),  meat  juice,  essence  of  beef,  and  good  potted  meats.  In  view  of  the 
comparatively  low  price  of  vegetables,  the  daily  diet  may  be  well  supplied  with 
acid  vegetable  potassium  even  in  the  feeding  of  prisoners  for  whom  but  a 
small  allowance  is  made.  Lately  the  diet  in  prisons  has  been  decidedly  im- 
proved by  the  addition  of  fish. 

It  is  more  difficult  to  prevent  scurvy  at  sea.  In  long  sea  voyages  the  supply 
of  fresh  vegetable-  is  soon  exhausted,  and  a  portion  is  likely  to  spoil.  But 
canned  vegetables  may  readily  take  their  place  without  decidedly  increasing 
the  cost,  owing  to  the  abundance  of  good  material  upon  the  market.  Upon 
long  trips  a  substitute  for  fresh  meat  is  furnished  by  meal  extract. 

On  many  ships  in  order  to  furnish  the  requirement  of  acid  vegetable  potas- 
sium, lemon  juice  is  regularly  given  to  the  crew.  In  the  English  marine  it  is 
obligatory  thai  the  crew  shall  receive  a  corresponding  amount  of  lime  juice 
in  a  mixture  of  ten  parts  of  lime  juice  to  one  part  of  spirits.  The  best  method 
is  to  carry  the  fresh  fruit  upon  the  trip,  and  prepare  lemonade  from  it.  Arti- 
ficial lemon  juice  is  sometimes  adulterated,  and  decomposes  very  readily. 
Nbrdenskjöld  advises  preserved  mulberries  for  expeditions,  as  these  are  said  to 
have  a  particularly  favorable  action.  Wale  believes  fresh  meat  (with  the 
blood)  to  be  the  most  efficient  antiscorbutic.  When  this  is  not  at  hand,  green 
or  canned  vegetables  and  lemon  juice  must  be  used.  Potatoes  and  milk  are 
also  advised,  as  well  as  cider  and  Moselle  wine. 

Great  stress  is  also  laid  upon  drinking-water  and.  if  aecessary,  this  must  be 
obtained  from  sail  water  by  distillation.  Nansen  advises  thai  in  Polar  regions 
the  ice  which  projects  above  the  surface  he  melted  for  drinking,  since  these 
part-  have  been  exposed  during  the  summer  to  the  rays  of  the  >un.  ami  have 
tn  a  great  extent  lost  their  .-alt.  lie  believe-  it  unnecessary  to  distil  this 
water  for  drinking  in  order  to  escape  the  danger  of  scurvy,  and  considers  tin1 
belief  erroneous  that  a  -mall  amount  of  -all  is  harmful.  Good  beer  (pine 
beer)  i-  useful  for  the  prevention  of  scurvy,  and  the  present  status  of  brewing 
make-  it  possible  to  take  large  amount-  of  inexpensive  beer  upon  long  Bea 
voyages. 

Pickled  meat,  a-  universal  experience  has  shown,  has  a  deleterious  effect, 
and  for  this  reason  it-  use  is  to  be  limited  as  much  a-  possible. 

In  regard  to  epidemic-  at  Bea,  the  condition-  of  Beafaring  in  modern  times 
have  changed  ;  steamers  have  greatly  shortened  the  voyages,  and  provisions  are 
carried  in  -mailer  quantity  than  formerly.  These  causes,  and  also  the  excel- 
lent naval  regulation-  in  which  England  ha-  Bhown  itself  superior  to  all  Bea- 
faring nations,  have  made  the  disease  bo  rare  in  the  English   Navy  that  in 


412  THE  HEMORRHAGIC  DIATHESES 

the  years  from  1856  to  1861  only  1.05  per  thousand  of  marines  were  attacked 
by  the  disease.  In  the  Austrian  Marine  the  number  of  affections  from  1863  to 
1870  =  1  per  cent.,  but  in  1871  and  1872  it  declined  to  0.34  per  cent.  In 
the  German  Marine  during  the  period  from  April.  1875,  to  March,  1880,  only 
16  cases  of  scurvy  and  76  cases  of  scorbutic  gum  affection  occurred,  these 
groups  collectively  giving  a  proportion  of  0.475  per  cent. 

The  occurrence  of  scurvy  upon  ships  depends  neither  upon  sailing  in  north- 
ern nor  in  southern  latitudes,  in  this  nor  in  that  season,  but  particularly  upon 
the  supply  of  provisions  in  proportion  to  the  length  of  the  voyage.  This 
readily  explains  why  conditions  are  more  unfavorable  upon  sailing  ships  than 
upon  steamers.  In  the  former  only  the  most  careful  ship  hygiene  can  prevent 
an  outbreak  of  the  disease,  and  upon  such  ships  general  hygienic  conditions  are 
still  unsatisfactory. 

Besides  proper  kinds  and  sufficiency  of  food,  general  hygiene  is  most  impor- 
tant in  prophylaxis,  particularly  perfect  cleanliness  of  body  as  well  as  of  hab- 
itation, avoidance  of  excesses,  protection  against  cold,  etc.  Isolation  of  the 
patients  when  possible,  and  the  greatest  attention  to  cleanliness  on  contact  with 
them,  form  the  best  means  for  limiting  the  spread  of  the  disease,  that  is,  for 
arresting  it.  Too  much  stress  cannot  be  laid  upon  exercise  in  the  open  air,  by 
which  the  psychical  condition  of  the  patients  is  improved.  Where  a  change 
of  residence  is  possible  we  should  always  take  advantage  of  it. 

I  should  like  to  mention  a  few  points  of  importance  from  the  interesting 
book  of  Nansen,  "  Farthest  North,"  which  reports  one  of  the  greatest  sea 
voyages  of  all  times,  in  which  during  three  years  no  case  of  scurvy  occurred. 
In  regard  to  provisions  he  holds  the  view  that  in  prolonged  Arctic  expeditions 
meat  and  fish  that  have  been  preserved  by  salting,  smoking  or  incomplete 
drying  are  to  be  regarded  as  objectionable,  and  are  to  be  rejected.  The  lead- 
ing thought  in  provisioning  must  be  to  preserve  the  food  either  by  careful  and 
complete  drying,  or  by  sterilization.  "  What  I  wished  to  attain  was  to  have 
not  only  a  nourishing  and  wholesome  stock  of  provisions,  but  to  see  to  it  that 
there  was  as  much  variety  as  possible.  We  took  fish  of  all  sorts  in  hermetically 
closed  tins,  dried  fish  and  preserved  fish,  potatoes,  dried  as  well  as  in  tins, 
all  sorts  of  dried  and  preserved  vegetables,  cooked  and  dried  fruit,  preserves 
and  marmalade  in  large  amounts,  sweetened  and  unsweetened  condensed  milk, 
preserved  butter,  dried  soups  of  various  kinds,  etc.,  even  bread,  dried  vegetables, 
etc.,  in  zinc  cases.  As  drink  we  used  at  breakfast  and  in  the  evening  choco- 
late, coffee  and  tea,  occasionally  milk.  For  supper  at  first  beer,  later  lemon 
juice  with  sugar  or  syrup.  Aside  from  beer  and  some  malt  extract  the  expedi- 
tion had  no  alcoholic  drinks.  Occasionally  a  grog  was  made  from  mulberries 
or  other  fruit  syrup  with  the  addition  of  some  spirits/'  Meat  and  fish  were 
carried  in  a  desiccated  condition,  free  from  fat,  cartilage,  etc.,  and  mixed  with 
kidney  fat.  also  Vaage's  fish  flour;  flour  (previously  stewed),  so  that  it  could 
be  eaten  without  further  preparation ;  dried  cooked  potatoes,  pea  soup,  choco- 
late, bread  (carefully  dried,  hard,  wheat  bread)  and  aleuronat  bread  (wheat 
flour  with  30  per  cent,  of  aleuronat)  and  butter. 

It  may  be  interesting  to  quote  the  menu  of  the  25th  of  December,  1803: 
1.  Oxtail  soup,  2.  Fish-pudding,  with  potatoes  and  melted  butter,  3.  Eeindeer 


HEMOPHILIA  413 

roast  with  peas,  French  beans,  potatoes  and  preserved  cranberries,  4.  Mulber- 
ries with  cream,  5.  Cake  with  marchpane. 

The  general  treatment  of  scurvy  is  entirely  analogous  with  the  prophylactic 
diet.     Warm  baths  often  have  a  favorable  action. 

Special  treatment:  In  the  drug  treatment  of  scurvy,  cochleariae  has  long 
been  prominent.     A  formula  greatly  employed  is: 

I£  Herb,  cochl.  rec.  cone 50. 0 

Sem.  sinap.  cont 12.5 

Yin.  gall,  alb 300.0 

Macera  per  biduum,  colat.  adde  spir.  seth.  chlor G.O 

M..  D..  S. :  Half  a  wine-glassful  three  times  daily. 

There  are  further  employed:  Astringents,  such  as  tonica  amara.  and  aro- 
matics,  such  as  tannic  acid,  quinin,  cascarilla,  myrrh,  ratanhia,  calamus,  and 
gentian. 

The  employment  of  beer  yeast,  pure  or  with  the  addition  of  water  and 
sugar,  ää  200  to  300  gram-,  daily,  is  very  popular. 

Disease  of  the  gums  is  be>t  prevented  by  the  early  removal  of  all  carious 
teeth  and  deposits  of  tartar:  later  this  is  not  so  feasible,  and  the  affection  of 
the  gums  must  then  be  treated  locally  with  astringent  solutions.  Tincture 
of  myrrh,  potassium  chlorate  and  potassium  permanganate  in  weakened  solu- 
tion are  especially  employed. 

In  scorbutic  cutaneous  ulcers,  poultices  containing  potassium  permanganate 
in  solutions  of  1  to  300  and  bandages  are  serviceable. 

Hemorrhages  are  treated  by  styptic-  and  tampons,  as  well  as  by  ergot. 
Surgical  interference  may  be  very  dangerous;  even  simple  bandages  thai  cause 
pressure  may  bring  about  <\rr\)  tissue  hemorrhages  and  deep  ulcerations. 

In  case  of  constipation  all  purgatives  which  have  a  decided  action  are  to  be 
avoided  unless  absolutely  necessary.  The  bowels  must  be  opened  by  the  cau- 
tious administration  of  enemata,  or  by  the  employment  of  the  mildest  laxative-, 
such  as  tamarind-,  for  by  the  too  active  stimulation  of  peristalsis  fatal  intes- 
tinal hemorrhages  may  be  produced.  In  the  treatment  of  such  bleeding  little 
or  nothing  is  gained  with  styptics  such  as  ergot  and  sesquichlorid  of  iron;  ice 
externally  or  internally  serves  the  purpose  best. 

HEMOPHILIA   (BLEEDER'S    DISEASE) 

By  the  term  hemophilia  we  mean  a  peculiar  hereditary  anomaly  of  con- 
stitution, characterized  on  the  one  hand  by  traumatic  hemorrhages  of  extraordi- 
nary stubbornness,  and  on  tl ther  hand  by  a  conspicuous  tendency  to  spon- 
taneous and  repeatedly  recurring  hemorrhages,  for  which,  up  to  the  present 
time,  no  plausible  anatomical  substratum  has  been  determined.  Combined 
with  this  is  a  marked  predisposition  to  " rheumatic "  affections  which  is  mani- 
fested by  painful  arthritic  swellings.  In  the  recognition  of  the  disease,  the 
congenita]  and  hereditary  factors  must  be  considered  as  well  as  the  habitual 
tendency  to  bleeding,  and  in  the  present  conception  of  the  disease  these  two 
peculiarities  dominate  the  clinical  picture.    They  form  a  basis,  too,  for  the  dif- 


414  THE  HEMORRHAGIC  DIATHESES 

ferentiation  of  hemophilia  from  related  clinical  pictures  which  are  included  in 
the  conception  of  the  hemorrhagic  diathesis,  i.  e.,  from  scurvy  and  morbus 
maculosus  Werlhofii.  The  former  differs  from  hemophilia  decidedly  by  the 
fact  that  it  is  rarely  sporadic,  but  usually  endemic  or  epidemic.  Still  more 
characteristic,  however,  is  its  dependence  upon  external  conditions ;  it  is  the 
expression  of  severe  disturbance  of  nutrition  produced  by  obscure  diseases  or 
by  long-continued  insufficient  and  improper  nourishment.  Morbus  maculosus 
■Werlhofii  differs  from  hemophilia  particularly  in  that  it  unquestionably  belongs 
to  the  acquired  diseases,  in  which  the  factor  of  heredity  plays  no  part.  This 
affection  is  never  congenital  as  is  the  case  with  hemophilia,  and  this  differential 
peculiarity  also  applies  to  scurvy.  Unlike  the  scurvy  patient,  the  bleeder  is  fre- 
quently well  nourished  and  strong,  and  except  for  his  tendency  to  spontaneous 
hemorrhages  he  might  almost  be  considered  healthy. 

In  comparing  hemophilia  with  related  diseases  in  the  group  of  the  hemor- 
rhagic diatheses,  one  peculiarity  of  hemophilia  stands  out  prominently.  In 
contrast  with  what  is  found  in  the  diseases  previously  named,  it  is  not  a 
pathologic  process  but  a  permanent  condition  which  manifests  itself  sometimes 
after  recognizable  causes  (traumatic  hemorrhages),  at  other  times  following 
unknown  ones  (spontaneous  hemorrhages).  For  this  reason  hemophilia  has 
been  designated  as  a  "  vitium  primae  formationis." 

Hemophilia  is  probably  in  all  cases  a  congenital,  and  also  a  hereditary  con- 
dition. The  intensely  hereditary  character  of  this  pathologic  condition  has 
been  from  the  earliest  times  a  source  of  great  interest.  Grandidier  calls  it 
"  the  most  hereditary  of  all  hereditary  diseases."  Only  very  exceptionally  is 
a  single  case  of  hemophilia  observed  in  a  family.  The  most  striking  point  is 
the  frequency  of  the  cases  in  one  and  the  same  family.  From  a  study  of  the 
total  number  of  known  hemophilia  cases  and  their  distribution  in  individual 
families,  it  may  be  noted  that  in  every  family  of  bleeders  there  are  at  least 
three  bleeders.  Sometimes  the  transmission  is  immediate  from  the  parents 
to  the  child.  Much  more  frequently,  however,  the  transmission  of  the  disease 
follows  a  peculiar  law  of  heredity,  peculiar  because  it  reveals  ä  remarkable 
sex  difference  in  the  frequency  with  which  hemophilia  is  acquired  and  trans- 
mitted. Females  show  a  greater  tendency  to  transmit  the  disease;  while, 
in  contrast  to  this,  in  the  male  sex  a  predisposition  to  acquire  the  disease  is 
prominent.  The  latter  predisposition  is  evident  from  the  fact  that  the  major- 
ity of  bleeders  are  of  the  male  sex.  The  tendency  of  the  female  to  transmit 
hemophilia  is  characterized  by  another  peculiarity.  A  woman  from  a  bleeder 
family  may  transmit  hemophilia  to  her  offspring  without  herself  being  hemo- 
philic, the  disease  skipping  a  generation.  This  order  of  transmission  is  indeed 
the  rule.  Formerly,  when  fewer  reports  of  cases  were  at  hand,  it  was  believed 
that  only  males  were  affected  by  the  disease,  females  being  exempt,  and  that 
it  was  women  exclusively  who  transmitted  the  disease.  On  this  assumption 
first  the  laity  and  subsequently  also  scientists  designated  the  women  in  families 
of  bleeders  as  "  conductors."  Close  investigation  and  increasing  experience 
have,  however,  taught  us  that  females  also  may  be  attacked  by  hemophilia, 
although  far  less  frequently  than  males.  For  every  thirteen  males  there  is 
one  female  bleeder.     The  view  that  women  exclusively  transmit  the  disease 


HEMOPHILIA  415 

can  no  longer  be  strictly  maintained  on  account  of  many  exceptions  to  this 
rule.  Grandidier  has  described  the  predisposition,  transmissibility,  and  the 
hereditary  sequence  in  hemophilia  in  the  following  paragraphs : 

1.  Men  from  families  of  bleeders  who  are  bleeders  themselves,  whose 
wives  are  not  descended  from  bleeder  families,  by  no  means  always  beget 
hemophilic  children;  on  the  contrary,  in  these  ruse*  the  children  are  frequently 
healthy  with  no  tendency  to  the  disease.  Vice  versa,  however,  it  appears  that 
hemophilia  quite  invariably  appears  among  the  children  of  women  who  are 
bleeders. 

2.  Men  descended  from  bleeder  families  without  being  Heelers  themselves, 
and  whose  wives  are  from  normal  families,  rarely  beget  hemophilic  children; 
on  the  other  hand,  women  belonging  to  bleeder  families  who  ore  not  themselves 
bleeders,  give  birth  almost  invariably  In  children  who  suffer  conspicuously  from 
hemophilia. 

On  account  of  the  gravity  of  hemophilia,  its  continuity  in  families,  and 
the  fatal  outcome  which  is  usually  due  to  severe  hemorrhage,  also  because  of 
popular  interesl  and  the  mysterious  character  of  the  affection,  it  is  natural 
that  record-  regarding  bleeder  families  extend  far  back  into  the  past. 

Grandidier,  in  his  well-known  monograph,  cites  200  bleeder  families  with 
609  male  and  18  female  bleeders  (=13  to  1).  In  the  bleeder  family  de- 
scribed by  Stahel  there  were  24  males,  all  bleeders,  in  four  generations.  Al- 
though females  an-  much  more  rarely  attacked  by  the  disease  than  males,  yet 
transmission  mos!  certainly  occurs  through  the  female  members  of  the  family. 
In  Bollinger's  collection  of  cases  it  appear-  to  be  the  rule,  as  in  color-blindness 
(Daltonism),  that  the  sons  of  women  whose  fathers  were  bleeders  are  most 
liable  to  hemophilia. 

Otto  and  Nasse  have  published  reports  regarding  the  tir-t  recorded  bleeder 
families.  Among  those  that  have  become  especially  well  known  are  the  fam- 
ilies a!  Tenna  in  Graubündten,  the  American  family,  Appleton-Browe,  and  the 
Mampel  family  at  Kirehheim  near  Eeidelberg,  whose  genealogical  tree  was 
firs!  described  by  Chelius  in  the  war  L827,  then  by  Mutzenbecher  in  is  II, 
and  lately  by  Lossen  (  Fig,  ■'.'D.  Thi-  ancestral  tree  shows  that  the  tendency 
to  bleed  is  transmitted  exclusively  through  the  female  members  of  the  family 
who  themselves  without  exception  remained  unaffected,  a  peculiarity  which 
we  -hall  later  discuss  in  another  affection,  hereditary  Daltonism.  Vice  versa, 
from  marriages  between  male  bleeders  and  female  non-bl lera  healthy  chil- 
dren are  horn. 

Worthy  of  note  also  is  the  proportion  between  hoys  and  girls  in  the  vari- 
ous generations:   In  the  firsi   generation   from  the  common  ancestors,  there 

are  four  hoy- ami  two  girls ;  three  of  these  boys  (or  75  percent.)  are  bl lers, 

hut  none  of  the  girls.  In  the  second  generation  there  are  1  I  boys  and  '.'  girls; 
of  the  former  L3  (or  '.»■':  per  cent.)  are  bleeders,  of  the  latter,  none.  Finally, 
in  the  third  generation,  among  at  leasl  50  children,  there  i-  only  one  bleeder, 
a  male  who  was  the  offspring  of  a  non-bleeder  mother  belonging  to  the  same 
ascending  line.  There  i-,  therefore,  a  conspicuous  diminution  of  the  disease 
in  the  thud  generation,  and  tin-  i-  probably  due  to  intermarriage  with  healthy 
families. 


416 


THE  HEMORRHAGIC  DIATHESES 


Another  tree  of  a  well-marked  bleeder  family  was  described  by  M.  Fischer 
in  1889  in  his  dissertation  on  this  disease.  This  family,  comprising  more 
than  four  generations,  lived  in  a  village  in  Württemberg,  and  though  otherwise 
not  of  distinction  was  characterized  by  a  few  remarkable  facts.  Thus  the 
apparent  male  ancestor  who  was  a  bleeder  (he  married  twice,  one  wife  evi- 
dently not  being  hemophilic,  there  being  bleeders  among  the  children  of  both 
marriages)  himself  directly  transmitted  the  predisposition,  whereas  this  is 
ordinarily  the  case  only  with  the  female  members  of  the  family.  Further- 
more, among  the  female  "  conductors,"  there  were  two  who  were  themselves 
bleeders,  which  is  contrary  to  the  rule.  On  the  whole,  among  114  members  of 
the  family  there  were  17  bleeders,  13  males  and  4  females,  the  implication  of 
the  female  sex  being  excessively  high.  The  length  of  life  of  these  bleeders 
was  from  nine  months  up  to  sixty-two  years.  In  most  members  of  the  fam- 
ily, especially  among  the  bleeders,  there  was  another  pathologic  predisposition, 
namely,  to  rheumatic  affections,  headache,  congestions,  and  affections  of  the 
teeth. 

Only  continuous  and  prolonged  study  of  the  genealogical  history  of  a 
bleeder  family  will  reveal  whether  the  disease  is  likely  to  assert  itself  for  a 
longer  time,  or  whether  the  tendency  is  so  diminished  in  the  mothers  of  the 
third  generation  that  it  will  no  longer  betray  itself. 


Fig.  22. — Genealogical  Tree  of  the  Bleeder  Family  Mampel.     (After  Lossen.) 

Bleeders  are  shaded. 


GUIDE  TO   FIGURES  22,  23,  24,  AND  25. 
(~\  female  descendants  ] 


D 


+ 


well 


male  " 

female  " 

male 

died  from  hemorrhage 


bleeder 

Daltonist 

hemeralops 


HEMOPHILIA 


417 


The  fact  that  hemophilia  may  be  directly  transmitted  also  by  the  ?nale 
descendants  forms  an  exception  to  the  rule  that  women,  even  healthy  women, 
transmit  the  disease,  that  is,  act  as  conductors.  In  a  family  in  Bremen  the 
affection  was  transmitted  by  the  father  to  the  male  members  through  three 
generations.  Also  in  the  bleeder  family  from  Wald  in  the  Canton  Zurich 
such  a  tendency  is  noted,  while  on  the  other  hand,  the  transmission  from  the 
healthy  mother  occurs  in  the  sons.  In  this  case,  in  the  first  generation  that 
showed  bleeders,  among  16  persons  there  were  7  bleeders.  In  the  following 
generation,  among  28  members  there  were  16  bleeders.  In  the  third  genera- 
tion, there  was  a  noteworthy  decrease  in  that  this  showed  only  1  bleeder  and 


+  + 

Fig.  23. — Genealogical  Tree  of  a  Bleeder  Family.     (After  II.  Gocht.) 
Bleeders  are  shaded. 

12  non-bleeders.  That  from  a  hemophilic  mother  bleeders  as  well  as  non- 
bleeders  may  be  born  is  demonstrated  by  the  following  ancestral  tree  which  is 
taken  from  a  communication  of  H.  Gocht  (Anh.  f.  Min.  Chir.,  Bd.  59) 
(Fig.  23). 

The  disease  proved  itself  most  stubborn  in  a  family  in  the  little  village 
of  Tenna  in  Graubündten,  consisting  of  aboul  170  persons,  whose  family  tree 
was  firai  described  by  Grandidier  and  Vieli,  and  then  carefully  revised  by 
Eösli  who  eliminate«!  many  incorreel  statements  of  the  firsl  communication. 
Eere  the  hereditary  transmission  could  be  followed  through  sis  or  seven  gen- 
erations. However,  bleeders  twice  married  into  the  family,  which  may  explain 
the  long  persistence  of  the  pathologic  predisposition.  Several  times  the  dis- 
ease skipped  two  generations  in  this  family,  then  reappeared  in  the  third.  In 
the  direct  descendancy  -till  longer  pauses  occurred;  but  probably  only  the 
severesl  cases  have  been  recorded. 

The  disturbances  to  which  we  may  ascribe  hemophilia  may  be  designated 
as  u pardblastic"  if  we  with  Eis  ascribe  the  developmenl  of  the  connective 
tissue  and  of  the  blood  and  lymph  apparatus  to  the  parablasts  in  opposition 
to  the  archiblasts,  ibis  latter  designation  being  reserved  for  the  epithelial 
tissues  that  compose  the  ectoderm  and  the  entoderm. 

Although  the  developmenl  of  the  parablasts  may  still  be  questionable, 
88 


418  THE  HEMORRHAGIC   DIATHESES 

and  it  may  not  be  as  yet  quite  certain,  as  His  assumes,  that  this  is  an  exclu- 
sively maternal  formation,  still  pathology  furnishes  a  number  of  remarkable 
facts  emphasized  by  Klebs,  which  assign  to  the  connective  tissue  germ  ("  para- 
blasts")  a  definite  position  in  the  structure  and  economy  of  the  body.  As  to 
the  controversy  in  regard  to  the  origin  of  the  parablasts  and  their  comparison 
with  the  archiblastic  tissue,  no  matter  how  it  may  be  decided,  His  has  proven 
the  entrance  of  the  parablastic  endothelia  into  the  cavities  of  the  heart  and 
the  vessels  (a  view  which  has  been  given  new  support  by  Kölliker  and  by  0. 
Hertwig)  and  this  indicates  a  great  advance  in  pathology.  If  this  special 
position  of  the  parablasts  is  recognized,  quite  new  view-points  are  presented 
for  the  production  of  pathologic  predispositions  during  fetal  development,  to 
which  Klebs  particularly  refers.  For  it  may  be  proven  that  in  a  varying 
development  of  the  connective  tissue  extraordinarily  important  congenital  and 
pathological  processes  are  combined,  and  that  these  are  processes  in  which  the 
transmission  of  both  sexes  plays  throughout  a  very  different  role,  the  female 
element  representing  the  carrier  of  the  disturbance,  without  in  all  cases  par- 
ticipating in  the  disturbance  itself,  while  the  male  element  is  the  passive  part. 
We  might  be  inclined  from  this  general  fact  to  ascribe  to  the  parablasts  at 
least  a  predominant  feminine  nature,  as  might  easily  be  possible  if  they  actually 
arose  from  leukocytes  that  had  wandered  in.  As  this,  however,  has  not  yet 
been  proven  we  must  content  ourselves  with  looking  upon  the  parablast  as  a 
structure  upon  which  the  male  pronucleus  (sperm  cell)  in  the  main  has  a 
slight  influence,  much  less  than  the  female  pronucleus. 

We  incline  to  this  view  for  the  reason  that  individual  parts,  particularly  the 
bony  tissue,  by  reproducing  paternal  forms  from  the  parablastic  tissues,  as  is 
very  frequently  seen,  may  be  recognized 'as  under  the  influence  of  the  male 
pronucleus.  Nevertheless,  we  may  assume  that  in  certain  cases  this  influence 
is  much  less  operative  in  females  than  in  males,  and  thus  the  non-appearance 
of  the  disease  in  the  female  members  of  a  hereditarily  affected  family  may  find 
an  explanation. 

The  same  peculiarity  of  the  transmission  of  properties  through  the  mother, 
who  herself  may  show  no  traces  of  them,  is  observed  (as  may  be  mentioned  here 
in  passing)  also  in  other  disturbances  which  cannot  be  traced  exclusively  to 
the  parablasts,  such  as  hereditary  Daltonism.  In  this,  as  in  bleeder  families, 
the  law  of  transmission  to  the  male  descendants  is  seen,  as  was  mentioned  by 
Ribot  and  Darwin.  Horner  reports  two  very  conclusive  ancestral  trees,  the 
correctness  of  which  is  due  to  his  personal  knowledge  of  the  members  of  the 
family.    The  ancestral  tree  is  here  given  for  comparison  (Fig.  24). 

This  affection  occurs  exclusively  in  the  male  descendants,  and  is  trans- 
mitted by  the  female  who  remains  free.  The  single  exception  of  a  transmis- 
sion from  father  to  son,  which  occurred  in  the  fifth  generation,  is  only  an 
apparent  one,  for  the  mother  belonged  to  a  collateral  line  affected  with  the 
same  defect.  It  is  noteworthy  that  from  this  marriage  a  great  number  of 
grandchildren  who  were  color-blind  were  begotten,  the  mothers  of  all,  corre- 
sponding to  the  law,  remaining  unaffected,  although  in  this  case  the  hereditary 
transmission  appears  to  have  attained  an  unusual  development. 

The  same  law  of  heredity  as  in  hemophilia  and  in  color-blindness  is  also 


HEMOPHILIA 


419 


operative  in  another  remarkable  affection — nifjlit-blindness  (hemeralopia). 
Although  this  disease,  strictly  considered,  is  not  within  the  realm  of  our 
theme,  nevertheless  it  is  so  interesting  that  this  slight  digression  is  permis- 
sible. Our  knowledge  regarding  the  etiology  of  night-blindness,  in  so  Ear  as 
heredity  is  concerned,  is  limited  to  the  following  points:  First,  that  hemeral- 
opia, if  it  is  hereditary,  attacks  more  men  than  women,  and  that  the  disease 
is  frequently  met  with  when  the  parents  are  blood  relatives;  further,  that  the 
disease  has  been  observed  in  several  children  of  the  same  family,  and  has  been 
followed  through  several  generation-,  from  four  to  six.  In  literature  we  find 
that  where  the  disease  has  appeared  in  successive  generations  partly  sons  and 
partly  daughters  were  attacked  (Sedan,  Recueil  d'ophthalm.,  1885:  Two  fam- 


ODD 


Fia,  24. — Genealogical  Tree  of  a  Family  showing  Daltonism.      (After  Horner.) 

I  >;iltonists  arc  shaded. 


dies;  in  the  firsl  there  are  only  12  members,  5  females  and  T  males,  that 
were  affected,  and  in  the  second  family,  of  9  that  were  affected,  5  females 
and  I  males.  Savenzy  (Irish  Hospital  Gazette,  1872)  reports  a  family  of  5 
brothers  and  5  sisters,  of  whom  2  brothers  and  :;  sisters  had  night-blindness)  : 
or  the  disease  may  attack  only  the  sons  in  a  generation,  and  in  such  cases  we 
occasionally  find  the  type  of  heredity  which  is  characteristic  of  hemophilia  and 
of  Daltonism. 

We  owe  to  E.  Amiiiann.  eye  specialisl  in  Winterthur,  the  knowledge  of  the 
faci  thai  night-blindness  is  transmitted  according  to  the  same  laws  as  hemo- 
philia and  Daltonism.  Ammann  reports  the  family  tree  of  a  hemeralopic  fam- 
ily from  which  the  law  of  heredity  may  he  determined  with  absolute  certainty 
(  Fig.  25).  At  the  Bame  time  the  observation  thai  night-blindness  and  myopia 
are  often  combined  receives  an  important  confirmation  from  the  fad  that 
he  determined  the  constanl  occurrence  of  both  these  affections  in  this  family. 

It  was  demonstrated  that  in  the  latter  family  only  the  hemeralopes  were 
nearsighted   (Ammann  found  nine  dioptrics),  while  the  members  who  were 


Fig.  25. — Genealogical  Tree  of  a  Hemeralopic  Family. 
Hemeralops  are  shaded. 


(After  E.  Ammann.) 


HEMOPHILIA  421 

not  attacked  by  night-blindness  showed  almost  normal  refraction.  If  we  con- 
sider the  genealogy  of  this  family,  which  is  shown  under  Fig.  25,  it  is  noted 
first  that  the  ancestor  of  the  family,  Andreas  St.,  born  in  1750,  was  healthy. 
Whether  he  was  the  son,  or  his  wife  the  daughter  or  sister,  of  a  person  who 
had  night-blindness,  cannot  now  be  ascertained.  His  three  sons  were  all 
night-blind,  but  did  not  marry.  His  daughter,  Mrs.  Lehmann- Steiner,  unfor- 
tunately became  the  ancestress  for  the  further  transmission  of  the  disease. 
She  transmitted  the  affection  to  her  two  sons:  of  her  two  daughters,  one 
(Mrs.  Vogel-Lchmann)  transmitted  the  disease  to  two  of  her  four  sons. 
Therefore,  not  all  of  the  sons  are  night-blind,  as  in  the  second  and  third  gen- 
erations, but  only  one-half  of  them  ;  of  the  four  married  daughters  only  two 
became  conductors  for  the  following  generation,  and  of  these  two  only  one 
transmitted  the  disease  to  her  two  sons,  while  the  other  (Mrs.  Frey)  had  three 
sons  of  whom  one  only  showed  the  disease.  The  four  daughters  of  Mrs.  Frey 
have  very  large  families,  but  the  sixth  generation  of  this  line  remains  com- 
pletely exempt  from  the  disease. 

Therefore  a  decided  diminution  of  the  disease  is  here  apparent,  as  had  been 
previously  observed  by  Cunier  in  the  year  1838.  The  condition  is  different  in 
the  families  where  the  disease  is  transmitted  from  the  male  side,  i.  e.,  from  the 
affected  father  through  the  daughter  to  the  grandchild:  Walter  Reifer,  the 
grandchild  of  Adolf  Vogel,  is  a  descendant  of  the  sixth  member,  and  inherits 
the  disease  to  so  high  a  degree  that  be  can  scarcely  go  about  alone  at  night. 
In  the  fifth  generation  also  there  is  a  grandchild  affected  by  night-blindness, 
in  whose  line  the  affection  perhaps  may  be  propagated;  therefore  the  disease 
may  not  rapidly  die  out  in  this  family,  but  it  is  certainly  on  the  decline.  It 
would  be  interesting  to  know  the  further  fate  of  the  family:  whether  a  mem- 
ber of  the  family  with  night-blindness  in  a  manifest  or  latent  form  may.  for 
some  unknown  reason,  become  the  progenitor  of  a  race  that  will  show  a  decided 
tendency,  or  whether  the  disease  will  gradually  disappear.  The  question  also 
interests  us  whether  the  affection  may  arise  spontaneously  without  any  hered- 
itary predisposition,  and  may  then  be  only  accidentally  transmitted  in  this  or 
that  way.  or  whether  such  sporadic  cases  as  are  actually  observed  depend 
upon  a  poorly  maintained  family  tradition,  or  upon  insufficient  observation 
of  the   individual    members  of  the   family.        To  decide  this,   further  accurate 

professional  observations  will  be  necessary. 

The  hereditary  form  of  hemophilia  is  unquestionably  and  by  far  the  most 
frequent,  but  a  so-called  congenital  form  of  the  disease  also  appears  to  exist. 
We  anderstand  by  this  that  from  the  marriage  of  healthy  persons  originating 
from  healthy  families  children  are  born  who  are  bleeders,  and  from  these  latter 
the  disease  may  be  further  transmitted. 

The  importance  of  marriage  between  blood  rrlnli<>n<  in  favoring  the  devel- 
opment of  hemophilia  has  been  emphasized,  a-  well  of  psychical  influences 
(sucb  as  fright,  anger)  during  pregnancy.  Dp  to  this  time  there  i-  no  sci- 
entifically founded  theory  in  Bupporl  of  these  views. 

Spontaneously,  and  withoul  heredity,  the  disease  certainly  occur-  only  in 

a   vei'v   -mall   number  of  cases,  and    in   the-«'  the  t  went  v--ec<>nd   year  of  life   is 

looked  upon  a-  the  absolute  limit  of  time  up  t<>  which  persons  previously 


422 


THE  HEMORRHAGIC  DIATHESES 


healthy  may  develop  symptoms  of  hemophilia.  These  conditions,  which  in 
themselves  cannot  be  accounted  for,  are  increased  in  importance  by  the  fact 
that  spontaneous  cases  of  "  hemophilia  "  which  develop  in  later  life  occur  only 
as  quite  localized  hemorrhages  limited  to  an  individual  organ. 

Regarding  the  geographic  distribution  of  the  disease  it  appears  that  Ger- 
many furnishes  the  main  contingent  of  cases;  yet  other  countries  are  not 
entirely  exempt  from  the  disease.  The  following  table,  compiled  by  Gran- 
didier,  gives  the  following  figures : 


Countries. 

Bleeder 
Families. 

Individual 
Bleeders. 

Bleeders. 
Males.           Females. 

Germany7 

93 
46 

20 
15 
7 
5 
3 
2 
1 
1 
1 

258 

141 

80 

61 

11 

48 

9 

9 

4 

3 

6 

236 

134 
75 

60 

7 
48 
6 
7 
4 
o 

5 

22 

England 

7 

France 

5 

North  America 

1 

Russia 

4 

Switzerland 

Sweden-Norvvav 

3 

Holland . .        

2 

Belgiu  m 

Denmark 

1 

East  India 

1 

Total 

194 

630 

584 
=92.6^ 

46 

=7.4$ 

The  actual  causes  of  hemophilia  are  entirely  unknown  to  us;  everywhere 
we  meet  with  hypotheses.  If  the  disease,  as  is  assumed,  be  a  parablastic 
disturbance  this  may  take  place  in  the  course  of  fetal  development  in  two 
ways;  either  in  a  greater  or  less  development  of  the  connective  tissue  germ 
or  because  individual  portions  of  this  structure  suffer  particularly.  Of  special 
importance  is  the  fact  that  it  is  the  maternal  element  which  transmits  the 
disease  without  being  itself  necessarily  involved,  this  property  being  an  inherent 
function  of  the  maternal  body,  and  much  more  marked  in  the  feminine 
descent  than  in  the  masculine.  This  faculty  can  exist  only  in  the  parablastic 
tissue,  and  especially  in  the  vascular  system  which  arises  from  it.  Conse- 
quently it  is  very  likely  that  the  parablast,  of  all  the  tissues  of  the  organism, 
is  most  influenced  by  the  mother,  being  less  subject  to  paternal  impressions 
than  any  of  the  other  constituents. 

There  are  two  factors  which  stand  out  prominently  in  the  investigation  of 
the  causes  of  the  disease:  the  structure  of  the  vascular  system  and  the  com- 
position of  the  l>l <n hI  itself.  As  hemophilia  is  not  to  be  considered  a  temporary 
but  a  permanent  pathologic  condition  which  is  congenital  and  hereditary,  we 
are  compelled  to  assume  a  disturbance  in  "the  first  formation,"  which  affects 
a  portion  of  the  connective  tissue  germ.  Nevertheless,  hypotheses  of  this 
nature  are  not  at  present  capable  of  verification  by  scientific  investigation; 
therefore,  in  regard  to  the  actual  condition,  we  have  been  compelled  \o  rely 
upon  the  scant  anatomical  findings  which  have  now  and  then  been  reported, 
but  which,  considered  collectively,  have  not  solved  the  puzzling  nature  of  the 
disease  in  question. 


HEMOPHILIA  423 

The  abnormal  composition  of  the  vascular  system  is  said  to  consist  in  the 
greater  tendency  of  the  vascular  walls  to  rupture,  and  this  has  been  thought 
to  be  due  to  a  peculiar  thinness  and  narrowness  of  the  arteries,  as  well  as  to 
their  very  superficial  situation.  Even  were  this  condition  more  common  than 
is  actually  the  ease,  these  vascular  alterations  would  not  sufficiently  explain 
the  spontaneous  hemorrhages,  for  we  find  similar  changes  in  the  narrowed 
aorta  of  chlorosis  but  no  hemorrhages.  In  discussing  the  pathological  anatomy 
we  shall  revert  to  this;  at  present  it  need  only  be  stated  that  some  investigators 
such  as  Hooper,  Liston,  Fischer  and  others  found  the  walls  of  the  arteries 
in  hemophilia  very  thin  and  showing  fatty  degeneration.  Yirchow  laid 
special  stress  upon  the  fact  that  in  a  bleeder,  aged  twenty-four,  the  aorta  was 
not  only  very  thin  and  elastic  but  also  very  narrow,  almost  of  infantile  dimen- 
sions, while  the  capillary  vessels  showed  no  change.  Elastic  arteries  which 
are  too  narrow  propel  the  blood  into  the  capillaries  with  too  greal  force,  and 
thi.-  circumstance  favors  the  hemorrhagic  diathesis,  or  at  least  the  continuance 
of  the  bleeding.  This  narrowing  of  the  arteries  cannot  be  ascribed  to  any 
special  disease  of  the  walls  of  the  vessel,  but  to  a  disturbance  of  development, 
analogous  to  the  condition  in  chlorosis;  this  is  consistent  with  another  special 
characteristic  of  hemophilia,  namely,  the  marked  hereditary  tendency  of  the 
affection.  Whether  the  fatty  degeneration  of  the  intima,  which  has  been  found 
in  some  cases  but  by  no  means  in  all,  is  not  rather  the  result  of  the  post- 
hemorrhagic anemia  than  the  cause  of  hemophilia  is  also  questionable.  At 
tin'  autopsy  of  some  cases  of  hemophilia,  hypertrophy  of  the  left  ventricle 
with  extreme  thinness  of  the  righl  has  been  found,  and  this  circumstance  has 
been  suggested  as  an  explanation  of  the  hemorrhages.  If  the  blood  be  pro- 
pelled with  great  force  through  the  narrow,  thin-walled  arteries,  the  increased 
pressure  of  the  hypertrophied  left  ventricle  may  cause  a  rapture.  Apart  from 
the  comparative  rarity  of  hypertrophy  of  the  left  ventricle,  it  must  he  remem- 
bered that  a  greal  number  of  the  hemorrhages  are  of  a  diapedetic  nature,  and 
cannot  he  referred  to  rupture  of  the  vessels  alone;  besides,  we  note  the  same 
symptom-complex  in  congenital  narrowing  of  the  aorta  without  the  sequence 
of  extensive  hemorrhages  such  as  frequently  recur  in  hemophilia! 

The  fallacy  of  these  mechanical  explanation-  became  more  evident  as  opin- 
ion- multiplied  that  an  insufficient  coagulability  of  Ihr  hl>>ml  was  the  cause. 
The  latter  conclusion  concerning  the  blood  was  the  resuU  of  experience  that 
in  hemophilia  all  hemorrhages,  even  with  the  most  Lnsignificanl  beginning, 
are  difficull  to  control.  The  hlo.nl  due-  coagulate,  however,  a-  may  be  seen 
from  the  surface  of  wound-;  spontaneously  it  forms  coagulated  masses  from 
beneath  which  new  quantities  of  blood  exude,  and  these  also  soon  coagulate, 
and  thus  enlarge  the  blood  clot  Gradually  the  oozing  of  blood  ceases,  and 
the  hemorrhage  is  arrested.  Sometimes,  however,  in  more  severe  hemorrhages, 
there  is  complete  cessation  of  the  production  of  the  fibrin  ferment,  the  blood 
gradually  loses  it-  power  of  coagulation,  the  hemorrhages  progressively  drain 
the  tissues,  and  death  results  from  excessive  loss  of  blood.  Any  form  of 
hemorrhage  may  he  fatal,  hut  this  is  mosl  frequent  in  epistaxis;  oext,  after 
extraction  of  teeth;  and.  occasionally,  in  intestinal  hemorrhages,  etc. 

Microscopic   ami    chemical    examination    i,(    the    blood    has    ßhown    normal 


424  THE  HEMORRHAGIC  DIATHESES 

conditions  in  by  far  the  great  majority  of  cases,  so  that  the  expectation  of 
finding  there  the  actual  cause  of  the  disease  has  not  been  realized.  Neither 
is  it  possible  to  determine  any  deviation  from  the  normal  in  the  amount  of 
salts  in  the  blood,  in  the  quantity  of  fibrin  producers,  in  the  corpuscular 
constituents  of  the  same,  in  the  numerical  relation  of  the  blood-corpuscles  to 
one  another,  or  in  the  amount  of  hemoglobin.  The  anticipation  of  finding 
the  amount  of  fibrin  decreased  is  also  unconfirmed;  Heyland  found  5  to  1,000, 
Gavoy-Eitter  2.6  to  1,000,  and  Otte  4.3  to  1,000.  In  the  numerous  contro- 
versies regarding  hemophilia  the  coagulability  of  the  blood  continues  to  be 
the  main  and  interesting  question,  and  has  played  a  great  role.  While  some 
authors,  such  as  Grandidier,  Lossen  and  others,  found  diminished  coagulabil- 
ity of  the  blood,  according  to  other  authors  this  occurs  only  in  the  later  stages 
after  severe  hemorrhages  (Hoffmann,  "Text-Book  of  Constitutional  Dis- 
eases"). Grawitz  does  not  consider  these  findings  contradictory,  for,  under 
ordinary  circumstances,  after  prolonged  hemorrhage,  an  increase  of  coagula- 
bility occurs,  and  the  blood  which  exudes  last  in  hemorrhage  frequently  coagu- 
lates immediately.  Therefore,  the  slowing  of  coagulation  in  the  later  stages 
proves  conclusively  the  diminution  in  the  power  of  coagulation. 

These  theories  of  the  coagulation  of  the  blood  have  been  recently  confirmed 
by  Alex.  Schmidt,  and  applied  by  him  to  explain  the  conditions  existing  in 
hemophilia.  According  to  his  observations,  the  blood  of  a  patient  coagulated 
four  and  a  half  minutes  after  exuding,  and  in  consideration  of  the  amount 
of  blood  previously  lost  he  pronounces  the  time  preceding  coagulation  as  an 
abnormally  long  one.  In  his  patient  the  action  of  a  "  zymoplastic  substance," 
produced  by  him,  was  first  tested  for  its  power  in  increasing  coagulation;  it 
was  placed  in  a  test-tube  with  the  blood  of  a  hemophilic,  and  coagulation 
occurred  after  ten  seconds,  whereas  previously  the  time  was  four  and  a  half 
minutes.  Locally  applied  to  bleeding  gums,  as  soon  as  contraction  of  the 
vessels  and  a  momentary  cessation  of  bleeding  had  been  brought  about  by  an 
injection  of  cocain,  the  "  zymo-plasma  "  also  proved  an  excellent  styptic,  and 
therefore  holds  out  the  possibility  of  a  substance  which  may  be  used  to 
increase  coagulation. 

The  deterioration  of  the  blood  in  functionating  erythrocytes,  as  an  ex- 
planation of  the  hemorrhages,  which  Cohnheim  assumed,  is  absolutely  un- 
proven;  I  have  repeatedly  taken  specimens  of  the  blood  of  hemophilics  which 
had  been  stained  according  to  various  methods,  and  have  shown  them  to 
blood  experts  who  could  detect  nothing  abnormal  in  them.  Blood  counts  have 
repeatedly  shown  normal  conditions,  as  well  in  regard  to  the  erythrocytes  as 
to  the  leukocytes.  The  blood-plaques  are  said  to  be  increased  in  amount. 
My  own  experience  of  hemophilia,  which  in  all  amounts  to  four  cases,  has 
been  gained  by  the  same  methods  of  blood  investigation  which  we  employ 
in  all  other  blood  diseases.  In  two  cases  in  which  there  was  no  marked  anemia, 
no  definite  changes  were  found.  In  both  of  the  other  cases,  in  which  repeated 
hemorrhages  caused  severe  anemia,  the  patients  being  respectively  eight  and 
sixteen  years  of  age,  I  found  the  same  changes  as  in  cases  of  anemia  after 
acute  and  profuse  losses  of  blood;  namely,  conspicuously  pale  color  of  the 
erythrocytes,  absence  of  well-developed  rouleaux  formation,  decrease  of  hemo- 


HEMOPHILIA  425 

globin  (30  to  35  per  cent.,  according  to  Sahli),  macrocytes,  poikilocytes, 
microcytes,  increase  of  blood-plaques;  no  leukocytosis.  These  conditions  im- 
proved under  suitable  treatment  (good  nutrition,  fresh  air,  processes  for 
hardening  the  body,  avoidance  of  everything  detrimental  to  health).  I  should 
like  to  mention  here  that  frequent  inhalations  of  oxygen  did  not  show  the 
slightest  influence  upon  the  general  condition  or  upon  the  composition  of 
the  blood. 

G.  Cohen  reports  a  very  remarkable  blood  finding  in  a  bleeder  (Zeitschr. 
f.  him.  Med.,  Festschrift,  1890)  :  The  blood  was  almost  colorless,  did  not 
coagulate  upon  beating,  and  upon  standing  left  only  isolated,  friable,  white 
coagula  of  fibrin  of  the  size  of  a  bean ;  microscopically  the  well-known  poly- 
morphia  of  the  red  blood  cells  was  found,  such  as  occurs  in  anemic  conditions, 
but  no  rouleaux  formation. 

Various  theories  have  been  proposed  in  literature  as  to  the  origin  of  hemo- 
philia. Among  the  best  known  that  of  Immermann  is  the  most  important 
and  most  widely  circulated.  It  depends  upon  certain  views  of  Virchow  to 
which  we  have  already  in  part  referred,  but  to  which  we  must  now  recur. 
Immermann  expounds  this  theory  in  the  following  way: 

Hemophilia  is  a  form  of  the  hemorrhagic  diathesis  which  is  chiefly  charac- 
terized by  a  hereditary  predisposition1  and  a  habitual  manifestation;  the 
hemorrhages  which  are  readily  produced,  frequent,  severe,  stubborn,  and  dan- 
gerous,  are  chiefly  caused  by  a  hereditary  and  habitual  disproportion  between 
tin-  blood  volume  inn!  the  capacity  of  the  vascular  apparatus,  which  result.-  in 
an  unusual  increase  of  secondary  pressure  in  the  latter.  Functional  erethism 
of  the  heart  and  unusual  development  of  its  muscles  may  in  some  cases  of  the 
affection  be  responsible  for  the  production  of  hemorrhages,  as  well  as  for  its 
abnormal  clinical  course,  and  for  the  tendency  to  fluxion  in  the  affected  indi- 
vidual; possibly  other  neurotic  influences  may  occasionally  arise  to  increase 
periodically  the  continuously  fluxionary  diathesis. 

Oertel  expresses  himself  likewise  regarding  the  nature  of  hemophilia,  lie 
i-  of  the  opinion  that  hemophilia  is  to  he  regarded  as  a  hydremic  plethora  of 

high  degree.     Following  tlie  same  train  of  thought  as   I  mmermann  and  Oertel, 

<i.  Cohen  (Zeitschrift  f.  him.  Med.,  Festschrift,  1890)  has  founded  a  general 
treatment  of  hemophilia,  the  main  objeci  of  which  is  to  combat  the  hydremic 
plethora  by  an  energetic  cataphoresis  and  diuresis.  The  decided  improvement 
which  Cohen  brought  about — this  refers  only  to  a  single  case--furnishea  some 
evidence  of  the  correctness  of  this  theory. 

Cohen's  patient  was  the  ninth  of  eleven  children  and  was  horn  in  1852; 
at  the  time  she  came  under  treatment  she  was  thirty-eight  years  old.  Her 
father  suffered  repeatedly  from  severe  epistaxis ;  twice  tampons  bad  to  he  used. 
A  grandchild  of  her  sister  Buffered  from  morbus  maculosus  with  effusion  of 
blood  into  the  joint-  and  renal  hemorrhages  and  died  of  this  disease  when 
twenty  years  of  age.  There  is  no  other  history  of  hemophilia  in  the  family, 
except  ;i  severe  hemorrhage  after  extraction  of  a  tooth  in  an  older  sister  of 
the  patient.    This  patienl  was  a  delicate  chlorotic  girl,  with  scant  menstrua- 

'  Differently  expressed:  "The  heredity  oi  certain  pathological  properties.11 


426  THE  HEMORRHAGIC  DIATHESES 

tion  and  without  tendency  to  hemorrhages.  A  far  more  decided  hereditary 
taint  was  noted  in  the  nervous  system;  the  father  was  a  person  easily  upset 
by  the  slightest  psychical  irritation,  e.  g.,  if  he  were  going  upon  a  journey, 
vomiting  and  marked  agoraphobia  would  occur.  He  died  of  heart  disease. 
One  sister  of  the  father  suffered  from  hysterical  spasms,  and  another  was 
very  "  nervous."  Among  the  children,  one  daughter  cannot  walk  upon  the 
street  without  an  attendant,  and  the  patient  in  question  suffers  from  cardiac 
palpitation  and  an  ill-defined  feeling  of  fear  unless  accompanied  by  her 
brothers  and  sisters.  In  this  patient's  twelfth  year  the  first  marked  hemor- 
rhage occurred  after  the  extraction  of  a  tooth;  a  few  months  later  menstru- 
ation began,  at  first  quite  regular  and  not  especially  profuse.  A  year  later, 
after  exertion  in  walking,  upon  the  fourth  day  of  the  period,  the  first  prolonged 
metrorrhagia  occurred,  with  syncope,  palpitation  of  the  heart,  nervous  attacks 
of  fear  and  excitement;  the  menses  now  became  irregular,  very  profuse  and 
prolonged.  During  her  attendance  at  school  attacks  of  epistaxis  were  first 
noted,  and  these  were  repeatedly  followed  by  spasms.  In  the  year  1869  the 
patient  was  bedridden  almost  the  entire  summer,  using  iron  waters,  whey  and 
baths.  She  was  in. bed  most  of  the  time  in  1870  on  account  of  frequent 
epistaxis  and  severe  uterine  hemorrhages;  for  the  first  time  marked  edema 
of  the  feet  was  present.  Toward  the  end  of  the  year  epistaxis  was  again 
severe.  In  1872  there  were  frequent  attacks  of  epistaxis,  but  injections  of 
ergotin  checked  the  hemorrhages  for  from  six  to  eight  weeks.  In  the  next 
year,  after  a  trifling  wound  of  the  finger,  hemorrhages  occurred,  lasting  for 
several  weeks.  Uterine  bleeding  was  almost  continuous.  Ergotin  was  of  no 
avail.  In  1871  hemorrhage  occurred  after  the  extraction  of  a  molar.  Two 
years  later,  following  a  very  severe  attack  of  dysentery  with  hematemesis  and 
enterorrhagia  such  a  severe  epistaxis  occurred  that  it  was  necessary  to  keep 
a  tampon  continuously  in  the  nose.  Later,  bleeding  from  the  nose  lasted 
several  hours.  Galvanization  of  the  sympathetic,  combined  with  ergotin  treat- 
ment, temporarily  improved  the  general  condition.  In  the  year  1881,  for  the 
first  time,  large  purpuric  spots  with  decided,  painful  swelling  appeared  upon 
the  left  upper  arm.  Menstruation  lasted  uninterruptedly  from  November  of 
the  same  year  until  February,  1882.  Vaginal  tampons  were  continuously 
necessary.  In  March,  1882,  for  the  first  time,  and  then  very  frequently,  there 
was  hemorrhage  from  the  uninjured  tip  of  the  finger.  During  January  of 
the  next  year  several  intact  fingers  and  the  nose  bled  daily.  Subcutaneous 
hemorrhages  followed,  the  blood  in  large  areas  of  the  right  thigh  and  of  the 
left  upper  arm  finding  its  way  through  the  skin.  In  1881  there  was  profuse 
diarrhea,  with  frequent  vomiting  accompanied  by  massive  hemorrhages,  and 
prolonged  elevation  of  temperature  which  lasted  for  months.  The  urine  be- 
came exceedingly  scant,  one-eighth  to  a  quarter  of  a  liter  in  twenty-four  hours ; 
it  was  pale,  free  from  albumin,  of  very  low  specific  gravity  (1.002  to  1.005. 
The  average  loss  of  blood  in  twenty-four  hours  amounted  to  one  pound  (358 
grams).  Galvanic  baths  decreased  the  number  of  hemorrhages.  Improvement 
was  brought  about  exclusively  by  treatment  based  upon  the  decreased  amount 
of  urine  and  an  energetic  diaphoresis  was  persistently  carried  out  for  over  three 
years;  injections  of  pilocarpin  which  for  a  time  were  substituted  by  packs 


HEMOPHILIA  427 

lasting  for  hours,  by  effusions  of  folia  jaborandi.  flor.  tiliae,  and  the  admin- 
istration of  large  doses  of  digitalis.  The  patient  was  cured  at  the  age  of 
thirty-eight  after  suffering  from  the  disease  for  twenty-five  years. 

In  the  study  of  the  etiolpgy  of  hemophilia,  those  who  adhere  to  the  Im- 
mermann-Oertel  theory  doubt  much  the  prominent  role  which  the  hereditary 
narrowing  of  the  aortic  system  is  said  to  play.  This  hereditary  anomaly  also 
produce.-,  chlorosis,  a  disease  which,  in  spite  of  the  similarity  of  individual  ana- 
tomical relations,  has  nothing  in  common  with  the  manifestations  of  hemo- 
philia. It  may  possibly  be  opposed  to  this  that  a  second  injurious  factor,  an 
abnormal  composition  of  the  blood,  is  added  to  the  smallness  and  narrow:  - 
of  the  vascular  system,  and  from  this  combination  hemophilia  arises,  or,  more 
correctly,  some  of  the  symptoms  of  the  affection.  In  opposition  to  this  is  the 
fact  that  the  examinations  of  the  blood  in  hemophilia  up  to  the  present  time 
have  shown  nothing  constant  nor  positive;  only  in  quite  isolated  instaj 
have  microcytosis,  macrocytosis,  poikilocytosis,  and  absence  of  rouleaux  for- 
mation been  observed.  Similar  deficiency  of  hemoglobin  in  the  erythroc 
and  in  the  total  blood  ha-  been  repeatedly  noted  in  anemic  individuals  after 
successive  hemorrhage-  (especially  of  a  traumatic  or  neoplastic  nature)  with- 
out the  tendency  to  an  acquired  hemorrhagic  diathesis,  so  that  a  characteristic 
or  pathognomonic  significance  cannot  be  ascribed  to  it.  All  hypotheses  which 
attribute  hemophilia  to  an  abnormal  composition  of  the  blood  are  lacking  in 
the  proofs  upon  which  a  scientific  proposition  should  he  based. 

That  hemophilia  is  a  neuropathic  diathesis  is  v.  Recklinghausen's  hypothe- 
H-  [Handbuch  der  Ml;/.  Pathol.  des  Kreislaufes  und  <l<  r  Ernährung).  In 
the  next  article,  when  describing  morbus  inaculosus,  we  shall  refer  more 
minutely  to  the  spontaneous  hemorrhages  «lue  to  the  vasomotors,  and  shall 
here  only  mention  that  this  author  ascribes  to  these  hemorrhages  (in  support 
of  his  theory)  the  prominent  aervous  symptoms  which  occur  in  certain  cases 
of  hemophilia  and  occasionally  in  entire  families  of  bleeders.  But  the  <pies- 
tion  arise-  whether  in  a  general  disease  such  as  hemophilia  the  spontaneous 
and  unexpected  manifestations  which  occur  may  not  naturally  keep  the  patient 
in  a  constanl  state  of  tension  and  expectancy,  and  thus  implicate  the  aervous 
system,  and  whether  or  not  the  nervous  disturbances  are  of  a  secondary 
nature. 

Finally,  we  must  mention  another  view,  already  referred  to  in  scurvy,  that 
hemophilia  is  a  toxic  infectious  disease.  This  is  the  opinion  of  \V.  Koch  of 
Dorpat,  I m t  it  ha-  received  hut  -light  attention  in  scientific  circle-.  Koch, 
in  his  hook  "Bleeder's  Disease  and  Its  Varieties,"  analyzes  the  evidence  on 
which  is  based  t  he  concept  ion  of  hemophilia  as  an  independent   affection.      II'' 

criticises  adversely  the  reports  of  the  disease  which  have  been  obtained  up 

to  the  present  time.  He  point-  out  how  faulty  these  are.  and  their  many 
contradictions.  The  conclusion  which  he  reaches  is,  approximately,  thai  hemo- 
philia is  ii'il  'Hi  independent  disease,  Iml  ihn!  il  is  mi  infectious  disease  and 
identical  with  scurvy.  "  I  believe/5  says  Koch,  "  that  the  blood  of  hemophilics 
exudes  through  the  walls  of  the  vessels,  which  give  no  evidence  of  anatomical 
change,  because  specific  toxin-  are  mixed  with  the  blood;  I  therefore  believe 
hemophilia  to  he  an  infectious  disease,  and.  on  account  of  the  coincident  symp- 


428  THE  HEMORRHAGIC  DIATHESES 

tomatology  and  pathological  anatomy,  I  believe  it  to  be  the  same  infectious 
disease  as  scurvy.  In  order  to  prove  its  parasitic  nature,  I  must  first  refer 
to  the  supposedly  congenital  form  of  hemophilia,  to  that  form  in  which  the 
symptoms  are  present  from  the  time  of  birth,  and  which  can  only  be  ascribed 
to  transmission  from  hemophilic  parents.  This  hereditary  condition  can  never 
be  explained  by  the  theory  of  a  pes  varus  congenitus  or  a  meningocele  con- 
genita, i.  e.,  by  a  vitium  primse  formationis  in  which  definite  observable  ana- 
tomical changes  (no  matter  how  complicated  in  origin  these  may  appear  to 
the  eye  of  the  observer)  result  in  disturbances  of  function.  For  nearly  a 
century  such  anatomical  conditions  have  been  sought  for  in  hemophilia,  and, 
in  spite  of  improved  methods  of  investigation,  only  vascular  anomalies  can 
now  be  found,  a  lesion  the  unimportance  of  which  admits  of  no  dispute,  par- 
ticularly as  in  only  a  few  cases  has  it  been  found.  In  opposition  to  this 
theory,  I  believe  congenital  hemophilia  to  be  quite  similar  to  congenital  syph- 
ilis, and  from  the  standpoint  of  infection  I  note  the  association  of  hemophilia 
with  wounds  and  ulcerative  processes  such  as  humid,  benign,  tuberculous  and 
syphilitic  skin  eruptions,  glandular  tuberculosis,  discharges  from  the  ear,  sup- 
puration of  the  navel,  etc. 

"  Some  hemophiliacs  have  a  marked  and  abnormal  desire  to  eat  sand,  earth, 
chalk,  peat,  acid  and  pungent  vegetables.  Some  have  febrile  attacks;  some 
perish  with  surprising  rapidity  after  only  slight  hemorrhage  or  other  localiza- 
tion; almost  all  have  an  enlarged  spleen.  I  lay  great  stress  upon  these  facts, 
as  well  as  on  one  which,  so  far  as  I  know,  has  not  yet  been  mentioned,  much 
less  discussed,  namely,  the  connection  between  hemophilia  and  infection.  Fur- 
ther we  must  consider  the  presumption  that,  in  those  hemophilic  families 
who  made  no  change  of  residence  for  generations,  particularly  if  the  hemor- 
rhages occurred  only  in  later  life,  the  process  may  often  be  referred  to  influ- 
ences of  the  ground  instead  of  to  heredity." 

Koch's  theory  of  hemophilia  as  a  toxic  infectious  disease,  both  as  a  whole 
and  in  its  premises,  is  so  purely  visionary  that  it  scarcely  appears  worth  dis- 
cussion. The  association  of  hemophilia  with  glandular  tuberculosis,  tubercular 
and  syphilitic  cutaneous  ulcers,  discharge  from  the  ear,  febrile  states  and  the 
other  pathologic  conditions  which  he  mentions  is  so  extremely  rare  as  to  be 
scarcely  noted  at  all  by  other  authors.  The  same  is  true  of  the  splenic  tumor, 
which  Koch  says  hemophiliacs  almost  invariably  show,  and  upon  which  he 
especially  bases  his  theory  of  the  infectious  nature'  of  the  disease.  Other 
symptoms  which  he  emphasizes  are  not  due  to  hemophilia,  but  to  the  anemia 
produced  by  the  hemorrhages,  as  is  the  case  with  neuropathic  symptoms. 
Above  all,  his  theory  of  an  infectious  etiology  is  untenable  inasmuch  as  the 
presence  of  pathogenic  agents  has  never  been  proven ;  all  investigations  as  to 
this  point  have  been  negative.  Still  more  unwarranted  does  it  appear  to  me 
to  ascribe  the  pathologic  processes  of  hemophilia  to  telluric  influences  instead 
of  to  heredity. 

Fully  as  I  agree  with  Koch  that  the  origin  of  hemophilia  cannot  be  looked 
for  in  purely  anatomical  causes — that  is  to  say.  be  dependent  upon  them — I 
cannot  concur  in  his  assumption  of  a  toxic  infection.  Even  if  this  could 
explain  the  nature  of  the  congenital  form  of  hemophilia,  it  can  never  explain 


HEMOPHILIA  429 

the  mystery  of  the  transmission  of  the  disease  in  a  hemophilic  family,  why  the 
mother  herself  should  remain  unaffected  while  she  transmits  the  disease,  why 
the  male  members  of  the  family  only  are  attacked,  why  men  from  bleeder 
families  do  not  beget  hemophilic  children,  whether  they  themselves  are  bleeders 
or  not,  etc.  Moreover,  congenital  hemophilia  is  much  rarer  than  that  form 
in  which  children  in  the  second  year  or  adolescents  manifest  the  signs  of  the 
disease!  Are  the  pathogenic  agents  latent  in  such  cases?  And  what  causes 
them  to  as.-ert  their  virulence? 

In  rare  cases  mothers  with  relapsing  fever  have  given  birth  to  children 
with  relapsing  fever !  This  is  probably  analogous  to  the  "  toxic  infection  " 
which  Koch  assumes  as  the  cause  of  congenital  hemophilia. 

In  the  last  few  years,  Kolb,  Babes,  Gartner,  Tizzoni  and  Giovannini  have 
demonstrated  bacteria  in  patients  suffering  from  purpura  hemorrhagica  as 
well  as  in  hemophilia  of  the  newborn;  these  bacilli  were  apparently  also 
pathogenic  in  animals,  and  upon  inoculation  produced  a  disease  characterized 
by  hemorrhages.  These  maladies  arc  probably  analogous  to  the  hemorrhages 
often  seen  in  other  infections,  and  we  may  assume  these  hemorrhages  to  be  due 
partly  to  local  changes  in  the  vessels  caused  by  collections  of  bacteria,  and 
partly  to  the  toxic  effect  of  bacterial  products.  These  may,  therefore,  to  some 
extent  be  classed  with  toxic  hemorrhages,  but  have  not  the  slightest  element 
in  common  villi  human  hemophilia. 

That  with  the  hemophilic  predisposition  Bevere  or  even  uncontrollable 
hemorrhages  follow  trifling  occasional  causes  such  as  never  produce  hemorrhage 
in  the  healthy  is  a  generally  well-known  fact,  and  thi-  has  led  to  a  differentia- 
tion between  spontaneous  and  traumatic  hemorrhage.  But  obviously  in  this 
division  the  conception  of  "trauma"  must  be  very  elastic.  The  hemophilic 
tendency  to  hemorrhage  shows  itself  during  the  period  of  physiologic  develop- 
ment, particularly  in  the  two  periods  of  dentition,  at  puberty,  and  at  the 
climacterium.  Even  in  tying  and  severing  the  umbilical  cord  we  sometimes 
produce  severe,  oven  fatal  hemorrhage,  and  we  recognize  by  this  and  other 
signs  the  hemophilic  predisposition  of  the  newborn. 

Severe  hemorrhages  from  the  gums  are  prone  to  occur  in  the  first  period 
of  dentition,  and  we  are  forced  to  look  upon  the  cutting  of  the  teeth  as  trauma. 
Quite  slighl  corporeal  punishment  may  produce  cutaneous  hemorrhages  and 
infiltrations  of  blood  out  of  all  proportion  to  the  nature  and  extent  of  the 
injury.  Blowing  the  nose  may  cause  oncontrollable  epistaxis;  profuse  con- 
junctiva] hemorrhages  may  be  produced  by  touching  the  eye.  Purgatives  may 
result  in  Bevere  intestinal  hemorrhages.  At  the  menstrual  period  and  in 
normal  labor  extraordinarily  Bevere  hemorrhages  have  been  observed. 

Especially  frequent  are  effusions  of  blued  into  the  joints. 

From  the  observations  of  Burgeons  it  i-  evident  thai  the  firsl  hemorrhages 
into  the  joints,  as  well  as  also  the  great  majority  of  the  later  one-,  are  caused 
by  external  conditions.  This  explains  why  children  are  not  attacked  by  hemor- 
rhages into  the  joints  before  they  learn  to  walk:  the  •'trauma"'  is  absent. 
I'.ul  when  they  first  begin  t<>  walk,  when  the  joints  are  utilized  and  the  entire 
muscular  Bystem  comes  into  action,  trauma  alter  trauma  occurs,  and  arthritic 
hemorrhages  arc  apt  to  appear.     We  quite  often  observe  Bevere  hemorrhi 


430  THE  HEMORRHAGIC  DIATHESES 

into  the  joints  which  occur  while  the  patients  are  in  bed,  and  when  we  are 
unable  to  detect  the  slightest  external  cause.  In  such  instances  we  are  almost 
always  dealing  with  joints  which  have  repeatedly  been  the  seat  of  effusions 
of  blood. 

Most  bleeders  perish  in  infancy,  a  large  proportion  before  the  eleventh 
year.  Earely  do  they  reach  old  age,  seventy  and  above.  The  hemophilic 
predisposition  diminishes  with  advancing  years. 

If  we  study  the  reports  up  to  the  present  time,  we  are  convinced  that  the 
true  causes  of  hemophilia  are  absolutely  unknown.  Even  of  the  two  etiologic 
factors  most  frequently  and  invariably  mentioned — an  abnormal  composition 
of  the  vascular  walls  (which  is  said  to  consist  in  great  fragility)  and  the 
insufficient  power  of  coagulability  of  the  blood,  to  which  I  shall  again  refer — 
we  do  not  possess  a  single  positive  proof  which  will  bear  criticism. 

Heredity  assumes  such  importance  in  the  etiology  of  this  disease  that  it 
is  well  to  point  out  that  a  highly  nervous  temperament  on  the  part  of  the 
ancestors  has  often  been  noted.  Of  course,  the  reports  of  the  patients  and 
their  relatives  must  be  accepted  and  utilized  with  extreme  caution ;  yet  a  num- 
ber of  well-authenticated  cases  are  on  record  which  certainly  prove  the  neuro- 
pathic predisposition  of  the  ancestors  of  bleeders. 

PATHOLOGICAL  ANATOMY 

The  anatomical  examinations  in  fatal  cases  of  hemophilia  have,  up  to  the 
present  time,  shown  nothing  that  is  characteristic  or  invariable ;  in  particular, 
very  little  has  been  revealed  to  explain  the  tendency  to  spontaneous  hemor- 
rhages, except  in  the  case  of  the  joints.  Here,  by  the  tireless  researches  of 
surgeons,  we  are  permitted  a  deeper  insight  into  the  mechanism  of  arthritic 
hemorrhages. 

The  number  of  autopsies  by  experts  on  the  cadavers  of  bleeders  is  very 
small ;  consequently  the  number  of  anatomico-pathological  findings  is  also  very 
scant.  In  general  the  following  is  reported :  The  cadaver  is  conspicuously 
anemic;  the  skin  is  waxy  pale.  In  cases  in  which  death  has  occurred  from 
hemorrhage  after  trauma,  petechia?,  ecchymoses,  suffusions  of  blood  and  signs 
of  injury  are  found  upon  the  skin  itself  with  comparative  frequency.  The  in- 
ternal organs  throughout  are  extremely  anemic.  The  small  amount  of  blood 
flowing  from  severed  vessels  is  decidedly  watery.  Of  the  abdominal  organs, 
in  which  there  are  often  signs  of  preceding  hemorrhages,  the  spleen  is  par- 
ticularly interesting;  W.  Koch  maintained — as  we  have  seen — that  it  is  in- 
variably enlarged;  it  has  occasionally  been  found  enlarged,  but  is  usually 
normal.  This  enlargement  of  the  spleen  in  hemophilia  has  sometimes  been 
deemed  especially  important,  particularly  as  proving  the  infectious  nature 
of  the  disease;  but  the  knowledge  that  this  finding  is  inconstant  has  led  to 
the  rejection  of  the  theory. 

The  blood-vessels  of  the  skin  which  are  superficially  situated  have  been 
often  described,  the  arteries  as  well  as  the  veins.  The  muscle  of  the  heart 
frequently,  but  by  no  means  invariably,  shows  fatty  degeneration.  Its  size 
has  in  some  eases  been  found  normal;  in  other  cases  it  is  hypoplastic,  and  in 
still  others  hypertrophic,  especially  as  regards  the  left  ventricle.     In  a  number 


HEMOPHILIA  431 

of  instances  the  large  arteries  and  their  first  branches  show  an  unusually 
narrow  lumen.  In  the  examination  of  the  structure  of  the  larger  and  -mailer 
arteries,  the  extremely  thin,  sometimes  actually  transparenl  condition  of  the 
intima  is  often  conspicuous.    Partial  fatty  degeneration  is  not  rarely  observed. 

Virchow  called  attention  to  the  smallness  of  the  heart  in  hemophilia,  to 
the  narrowness  and  thinness  of  the  walls  of  the  vessels,  which  is  similar  to  that 
in  chlorosis.  On  account  of  the  rarity  of  autopsy  reports  in  this  disease,  it  is 
highly  interesting  to  refer  to  this  finding  in  a  case  observed  by  Virchow.  upon 
which  he  held,  an  autopsy,  and  which  he  has  detailed  (Deutsche  Klinik.  1859, 
and  Canstatt's  Jahresb.,  1859).  "The  hlood,  as  in  other  cases  of  hemophilia, 
was  not  deficient  in  fihrin;  it  formed  a  decided  buffy  coat.  The  arteries  and 
veins  showed  no  large  ruptures — in  fact,  no  conspicuous  changes;  the  hemor- 
rhages, therefore,  must  have  been  from  the  capillaries.  The  veins  were  very 
wide,  the  arteries  very  elastic  and  narrow.  The  capillaries  and  nerves  showed 
no  decided  alterations.  In  the  central  part  of  the  vascular  apparatus  an 
abnormality  was  found  which  was  certainly  congenital;  the  thymus  gland  was 
still  very  large,  the  heart  pale  and  small,  the  aorta  narrow,  it-  walls  (hin  and 
very  elastic,  with  wavy  rises  due  to  slight  sclerosis  and  fatty  degeneration  of 
the  infinia,  particularly  in  the  descending  thoracic  aorta.  This  entire  finding 
closely  resembled  chlorotic  conditions  to  which  I  (Virchow)  have  previously 
called  attention.  The  development  of  the  heart  from  the  aorta  is  much  re- 
tarded in  chlorotics;  enlargement  of  the  heart  is  late  and  occurs  only  occa- 
sionally. Hemorrhage:-  are  \c\-y  frequent  and  severe  in  chlorotic-,  and  these 
can  probably  he  traced  to  the  arterial  changes  which  have  Keen  observed;  at 
all  events  the  round  ulcers  of  the  stomach  which  occur  chiefly  in  chlorotics 
certainly  bear  a  relation  to  individual  arteries.  There  i-  much  in  favor  of  the 
congenital,  or  at  least  very  early,  development  of  the  predisposition  to  chloro- 
.-i-;  and  this  may  he  positively  maintained  in  the  case  of  hemophilia.  The 
I. loud  collected  from  this  case  rapidly  decomposed,  depositing  xanthoglobulin 
crystals  a-  well  as  triple  phosphates  and  Leucin.  This  case  teaches  as  that  in 
hemophilia  it  is  not  an  unusual  fluidity,  a  dissolution  of  the  hlood.  which 
produce-  the  tendency  to  hemorrhage,  because  hlood  rich  in  fibrin,  just  as  in 
scurvy,  may  he  found  in  the  hemorrhagic  diathesis.  Nowhere  was  tendency 
to  rupture  of  I  he  blood-vessels  noted.  Therefore  the  question  arises  whether, 
in  thi-  case,  as  in  chlorosis,  the  narrowness  and  extreme  elasticity  of  the 
vessels  (arteries)  so  increase  the  blood-pressure  in  the  capillaries  that  a  pre- 
disposition to  rupture  and  consequent  hemorrhage  is  produced.  /"  this  case 
Ihr  cause  "f  the  hemorrhagic  diathesis  was  /"  be  sought  in  "  deficiency  <>f  //"■ 
vascular  formation,  and  it  i-  certainly  noteworthy  that  the  thymus  gland  had 
persisted  for  bo  long  a  time."" 

Virchow,  therefore,  considered  retardation  <>\  vascular  development  to  fie 
an  especial  pathologico-anatomical  sLrn  in  hemophilia.  Me  observes,  how- 
ever, that  exactly  the  same  conditions  a-  were  noted  by  him  in  hemophilia 
occur  al-o  in  chlorosis.  The  question  why  retardation  in  vascular  develop- 
ment causes  two  such  entirely  different  diseases  a-  chlorosis  and  hemophilia 

has  not  yet  I n  answered.     If  we  are  inclined  to  be  critical,  we  may  assume 

from  tin-  condition  of  affairs  that  retardation  of  vascular  formation  cannot 


432  THE  HEMORRHAGIC  DIATHESES 

be  the  detennining  cause  of  hemophilia.  Nevertheless,  the  descriptions  of 
Virchow  are  highly  important,  as  they  form  the  basis  of  the  Immermann- 
Oertel  theory  of  hemophilia. 

But  the  positive  findings  mentioned  above  which  have  been  observed  in  a 
number  of  autopsies  in  cases  of  hemophilia  are  opposed — few  as  they  are — by 
a  much  greater  number  in  which,  after  minute  investigation,  experienced 
pathologists  were  unable  to  determine  anything  noteworthy. 

More  widely  known  are  the  changes  in  the  bleeder's  joint,  a  knowledge 
of  which  we  owe  to  the  valuable  work  of  surgeons.  In  the  first  stage  of  the 
arthritic  disease,  we  find  the  symptoms  of  a  simple  effusion  of  blood.  The 
joint  cavity  is  filled  with  fluid  blood  and  dark  coagula  of  fibrin.  The  latter 
are  partly  free,  partly  adherent  to  the  walls,  and  by  proliferation  of  the  cell- 
layers  of  the  synovial  membranes  they  are  made  integral  parts  of  the  wall  of 
the  joint.  The  capsule  is  thickened,  shows  bloody  infiltration,  and  is  discol- 
ored. Moreover,  fibrin  deposits  are  found  upon  the  capsule  and  upon  the 
surface  of  the  cartilage,  causing  the  formation  of  brownish  pigmented  villi 
and  cartilage  proliferations.  If  the  effusion  of  blood  is  not  absorbed  the  joint 
swelling  remains,  and  inflammation  is  produced  which  pathologically  resembles 
the  condition  König  has  designated  as  hydrops  tuberculosus  fibrinosus.  The 
contents  of  the  joint  are  either  serous  or  hemorrhagico-serous,  and  of  a  light 
brownish  color.  The  perisynovial  connective  tissue  is  sclerotically  thickened. 
The  synovial  intima  shows  swelling  and  reddish-brown  or  brownish  discolora- 
tion, and  a  great  number  of  synovial  villi  of  a  brownish  tint.  The  blood 
coagulum  in  some  cases  attains  the  thickness  of  a  finger.  The  cartilage  has 
lost  its  white  color  and  its  luster,  and  appears  of  a  brownish  hue.  Coagulated 
masses  of  blood  are  found  in  layers  which  show  organization  and  connective 
tissue  change.  The  cartilage  is  partly  softened  by  the  disappearance  of  its 
upper  layer.  Continuous  small  and  large  depressions,  sharp-edged  and  map- 
like, invade  deeply  the  surface  of  the  bone  surrounding  the  cartilage.  The 
surface  of  the  cartilage  is  uneven  on  account  of  an  irregular  disappearance  of 
substance.  Following  this  second  inflammatory  stage,  a  third  occurs  in  which 
regenerative  changes  play  the  principal  role.  By  adhesion  of  the  joint  sur- 
faces, and  by  processes  of  shrivelling  in  the  soft  parts  and  capsules,  stiffness 
of  the  joints  supervenes.  The  joint  cavity  becomes  denuded,  the  joint  ends 
deformed ;  subluxation  takes  place ;  contracture  and  ankylosis  may  occur. 

Examination  with  the  Eöntgen  rays  has,  according  to  Gocht  (Arch.  f.  hi. 
Chir.,  1899),  given  constant  and  important  findings:  It  is  at  once  evident  that 
the  lower  end  of  the  femur  upon  the  affected  side  is  very  much  smaller  than 
that  of  the  opposite  side.  The  bones  upon  the  diseased  side  are  atrophic  and 
decidedly  too  permeable,  as  may  be  noted  in  the  lighter  color  of  the  Eöntgen 
picture — the  epiphysial  lines  upon  the  femur  and  the  tibia  lack  the  normal 
rounded  curves,  and  are  irregular,  often  serrated,  with  a  double  contour. 
While  upon  the  normal  side  a  broad,  open  space  marks  the  presence  of  normal 
cartilage,  and  the  osseous  ends  of  the  femur  and  the  tibia  present  their  well- 
retained  smooth  surfaces,  the  conditions  upon  the  diseased  side  are  quite 
different.  A  decreased  joint  space  is  found,  owing  to  destruction  of  the 
cartilage.     The  ends  of  the  bones  appear  completely  changed.     The  arthritic 


HEMOPHILIA  433 

portion  of  the  femur  is  serrated  and  irregular,  the  cavity  normally  existing 
between  the  two  condyles  has  been  obliterated;  the  same  is  also  true  of  the 
intercondylar  eminences  of  the  tibia  which  are  irregular  and  broadened.  Still 
more  advanced  lesions  are  seen  in  older  patients;  the  space  in  the  joint  car- 
tilage disappears  entirely,  the  tibia  seems  dislocated  toward  the  femur  out- 
wardly. Occasionally  adhesions  may  be  noted  between  the  femur  and  the 
tibia.  The  condition  of  the  capsule  cannot  be  accurately  determined  on 
account  of  the  effused  blood. 

The  microscopic  investigations  of  the  vascular  changes  in  hemophilia,  made 
by  Buhl  and  Birch-Hirschfeld,  deserve  attention. 

The  former  found  in  a  preacher,  aged  seventy-four,  suffering  from  chronic 
dermatoses  and  presenting  hemophilic  symptoms,  an  immoderate  growth  of 
the  capillary  vessel  loops  with  a  great  increase  and  subsequent  transformation 
of  their  nuclei.  Buhl  himself  does  not  believe  this  anomaly  to  be  peculiar  to 
hemophilia.  Birch-Hirschfeld  examined  the  heart  and  the  large  vessels,  a 
portion  of  the  spleen,  the  kidney  and  the  skin  of  a  child,  aged  one  year,  who 
had  succumbed  to  congenital  hemophilia,  and  remarks  concerning  these  organ- : 
"In  the  heart  and  in  the  vessels  connected  with  it  I  discovered  no  changes. 
It  may  be  stated  that  the  vessels  of  the  heart,  considering  the  age  of  the  child, 
were  quite  of  normal  size.  In  the  heart  muscle  there  were  but  slight  indica- 
tions of  fatty  degeneration.  The  valves,  as  well  as  the  intima  of  the  larger 
vessels,  were  delicate  and  normal  in  structure;  the  same  was  also  true  of  the 
muscularis  and  media  of  the  arteries.  In  the  kidneys  the  cortical  canals  were 
swollen  and  there  was  slight  granular  cloudiness  of  the  epithelium.  There 
was  Qothing  noteworthy  in  the  spleen  except  moderate  hyperplasia  of  the 
stroma  of  the  pulp.  But  I  must  mention — with  reserve — a  finding  which  I 
noted  in  the  capillaries  and  the  transitional  vessels  of  other  organs,  particu- 
larly of  the  liver  and  kidneys.  In  some  areas  the  endothelia  were  obviously 
enlarged,  their  nuclei  swollen;  here  and  there  were  granular  deposits  in  the 
protoplasm.  In  sonic  rather  poor  preparations  which  were  stained  with  silver, 
the  epithelial  arrangement  appeared  to  me  irregular,  disarranged,  with  occa- 
sional wide  spaces  between  the  endothelia.  1  do  not  lay  special  stress  Upon 
this  condition.  In  delicate  changes  of  this  kind  it  is  not  always  possible  to 
determine  how  much  is  artifact,  and  it  must  not  be  forgotten  that  such  changes 
are,  perhaps,  not  rare  in  the  1 ; i - 1  stages  of  other  chronic  cases."  Kidd  de- 
scribed in  the  finer  vessels  of  the  subcutaneous  connective  tissue  and  of  the 
muscles  an  increase  of  the  endothelia  with  dropsical  swelling  of  the  muscularis 
and  proliferation  of  their  nuclei — changes  which  Legg  in  another  case  was 
unable  to  recognize.  I  should  like  to  mention  the  simultaneous  occurrence 
of  hemophilia  wit h  mult iple  sarcomata. 

Obviously  pathological  anatomy  affords  no  clue  for  the  comprehension  of 
the  clinical  picture.  The  belief  that  blood  formation  is  periodically  increased, 
which  is  mentioned  by  some  authors,  has  Im t  little  to  3Uppori  it.  and  the  same 
is  true  of  the  hypothesis  that  the  overfilling  of  the  narrow,  perhaps  friable, 
vascular  system  of  hemophiliacs  by  a  hypertrophied  hear!  through  which  newly 
for I  blood  i-  occasionally  forced  in  large  amount-  leads  to  a  rupture  of  the 

markedly  distended  capillaries. 

2'J 


434  THE  HEMORRHAGIC   DIATHESES 


SYMPTOMATOLOGY   AND   COURSE 

The  phenomena  of  the  disease  are  quite  often  revealed  purely  by  accident; 
the  patients  are  attacked  either  spontaneously,  or,  in  consequence  of  very  slight 
injuries,  by  profuse  hemorrhages  or  such  as  are  very  difficult  to  control. 
Among  such  cases  I  wish  to  mention  the  hemorrhages  which  occasionally 
follow  ritual  circumcision,  and  sometimes  cause  the  surgeon  great  difficulty, 
as  well  as  those  which  occur  after  perforating  the  lobe  of  the  ear  for  earrings, 
and,  finally,  the  muscular  hemorrhages  which  occur  in  older  children  of  a 
hemophilic  predisposition,  when  they  are  chastised  by  the  teacher  in  school; 
these,  under  some  circumstances,  bring  the  guiltless  teacher  into  court. 

The  disease  shows  various  grades  of  development,  and  by  no  means  the 
same  intensity  of  symptoms  in  all  cases.  The  history  of  families  of  bleeders 
has  shown  that  in  individual  members  all  types  of  the  disease,  from  the 
mildest  rudimentary  forms  up  to  the  severest  ones,  may  be  found.  The  milder 
forms  are  characterized  by  an  evident  tendency  to  hemorrhages,  but  the  bleed- 
ing never  assumes  such  proportions  as  directly  to  threaten  life. 

In  nearly  three-fourths  of  the  cases  the  first  hemorrhage  occurs  before  the 
end  of  the  second  year,  and  the  latest  period  for  its  occurrence  is  the  twenty- 
second  year  of  life;  only  in  quite  isolated  cases  has  the  first  hemorrhage 
happened  at  a  later  age.  A  great  tendency  to  hemorrhage  is  noted  in  bleeders 
at  about  the  period  of  physiological  development.  Most  hemophiliacs  die  in 
the  first  year;  a  large  proportion  before  the  end  of  the  tenth  year.  Only  very 
rarely  is  old  age  reached — seventy  years  and  beyond.  Experience  teaches  that 
with  increasing  years  the  hemophilic  predisposition  declines,  until  finally  it 
disappears  entirely. 

As  has  been  stated,  the  physician  or  the  family  often  becomes  aware  of  the 
hemophilic  tendency  of  an  individual  quite  accidentally,  by  the  difficulty  of 
controlling  a  hemorrhage,  which  returns  again  and  again.  This  is  especially 
apt  to  be  the  case  if  the  patient  is  not  a  member  of  a  bleeder  family,  and  has 
not  older  relatives,  particularly  brothers,  in  whom  severe  hemorrhages  some- 
times occur  as  the  result  of  quite  trivial  injuries  while  at  play.  In  other 
cases,  surgeons  while  performing  operations  make  the  unpleasant  discovery 
that  the  hemorrhage  from  an  operative  wound  does  not  cease,  and  that  they 
are  dealing  with  a  bleeder.  The  hemorrhagic  or  hemophilic  predisposition  of 
the  newborn  is  earliest  recognized  if  hemorrhages  appear  after  severing  the 
umbilical  cord;  these  occasionally  are  uncontrollable,  and  result  in  the  death 
of  the  child.  However,  we  can  by  no  means  refer  all  hemorrhages  from  the 
cord  of  the  newborn  to  a  hemophilic  predisposition  of  the  child.  It  has  been 
proven  that  umbilical  hemorrhages  in  the  newborn  may  also  be  due  to  the 
influence  of  bacterial  blood  infection.  The  next  event  which  may  lead  to  the 
discovery  of  the  disease  is  ritual  circumcision,  which,  as  is  well  known,  is 
performed  upon  the  eighth  day  after  birth.  On  the  other  hand,  vaccination, 
according  to  usual  experience,  is  relatively  harmless.  The  disease  may,  how- 
ever, not  show  an  early  spontaneous  development  but  may  be  latent,  and  only 
appear  after  an  exciting  cause  and  upon  occasion.  The  most  common  time 
for  this  is  the  period  of  first  dentition,  and  thus  we  frequently  note  decided 


HEMOPHILIA  435 

signs  of  the  disease  in  the  form  of  severe  hemorrhages  from  the  gums.  Some- 
times in  girls,  although  quite  rarely,  there  may  be  no  evidence  of  the  disease 
throughout  infancy  and  childhood,  the  first  symptoms  appearing  at  the  time 
of  puberty  and  recurring  at  each  menstrual  period,  the  menses  being  unusually 
profuse  and  persisting  for  a  long  time.  Even  after  an  easy  and  uncomplicated 
labor  occasionally  severe,  even  fatal,  hemorrhages  occur,  so  that  Kehrer  has 
proposed  the  interruption  of  pregnancy  in  hemophilic  women  by  artificial 
labor. 

The  most  obvious  and  important  sign  in  the  clinical  picture  of  hemophilia 
is  the  appearance  of  well  marked  hemorrhages  cither  without  an  assignable 
cause  or  as  the  result  of  very  slight  external  injuries.  In  about  50  per  cent, 
of  the  cases  the  mucous  membrane  of  the  nose  is  the  seat  of  the  hemorrhages; 
next  follow  bleeding  from  the  gums  and  intestinal  hemorrhages  (each  about 
12  per  cent.),  then  pulmonary,  gastric  and  renal  hemorrhages  (each  about  6 
per  cent.).  Most  frequent  arc  the  hemorrhages  from  the  skin  and  mucous 
membrane,  next  from  the  joints,  to  which  I  shall  later  refer  explicitly,  and 
finally,  metrorrhagia.  Apart  from  arthritic  hemorrhages,  hemorrhages  from 
the  serous  membranes  without  assignable  cause  are  quite  rare.  On  the  other 
hand,  hemorrhage  from  the  conjunctiva  is  occasionally  noted,  apparently 
occurs  without  cause,  and  may  sometimes  be  so  severe  as  to  result  fatally. 
This  was  seen  in  the  case  of  two  brothers,  both  bleeders,  who  were  quite 
young.  Occasionally  the  hemorrhages  are  so  profuse  that  death  takes  place 
in  a  few  hours.  It  is  often  astonishing  to  observe  what  enormous  amounts 
of  blood  hemophiliacs  may  lose,  and  how  rapidly  they  recover  from  this.  In 
Cohen's  case  the  patient  lost  a  pound  of  blood  ( :'»r.s  -rams)  per  hour,  and  in 
another  case  of  hemophilia,  within  eleven  days  twenty-four  pounds  of  blood 
were  lost.  Occasionally  syncope,  the  resull  of  cerebral  anemia  whereby  blood- 
pressure  falls  to  a  minimum,  causes  a  cessation  of  hemorrhage.  With  an 
increase  of  the  blood-pressure,  hemorrhage  begins  anew.  The  disproportion- 
ately rapid  regeneration  of  the  blood  must  be  referred  to  the  previously  men- 
tioned increase  of  the  hematopoietic  function  of  the  bone-marrow  in  hemo- 
philia   (Fischer)    which,  however,  is  of  a  somewhat   hypothetical   nature. 

It  is  customary  in  hemophilic  bleeding  to  differentiate  between  spontaneous 
and  traumatic  hemorrhages.  All  hemorrhages  are  designated  as  spontane- 
ous for  which  no  plausible  reason  can  be  assigned.  P.ut  it  must  also  be 
considered,  in  the  study  of  the  hemorrhagic  diathesis,  that  there  are  condi- 
tions in  which  the  organism  of  the  hemophiliac  reacts  by  hemorrhages  to 
very  slighl  influences — influences  of  such  an  insignificant  character  that  the 
person  who  Buffers  a  lesion  scarcely  notes  it  at  all  or  but  very  slightly.  With- 
out doubt  some  of  the  hemorrhages  which  in  this  diathesis  have  been  looked 
upon  as  spontaneous  are  in  reality  traumatic.  We  differentiate  in  these 
hemorrhages  (spontaneous  as  well  as  traumatic)   two  form-:  The  superficial 

and    the   /'// Instil inl . 

Spontaneous  hemorrhages  are  occasionally  preceded  by  prodromes  such  aa 
cardiac  palpitation,  congestion  of  the  head,  vertigo,  tinnitus  annum,  anxiety, 
nausea  and  even  vomiting.  Prior  to  very  severe  hemorrhages,  decided  red- 
ness of  the  face  is  often  noted;  in  the  visible  arteries  rapid  and  strong  pul- 


436  THE  HEMORRHAGIC   DIATHESES 

sations  may  be  seen.  The  general  condition,  also,  is  decidedly  influenced ;  the 
patient  becomes  restless;  he  is  filled  with  fears  or  there  is  lassitude.  For 
a  lono-  time  the  fleeting  character  of  these  hemorrhages  has  been  noted.  After 
the  hemorrhage  has  ceased,  the  affected  persons  usually  feel  relieved  and  easy 
in  mind.  In  other  cases  these  premonitory  phenomena  are  entirely  absent. 
The  hemorrhages  may  come  on  without  any  noteworthy  prodromes.  Super- 
ficial spontaneous  hemorrhages  occur  most  frequently  from  the  mucous  mem- 
branes ;  first  from  the  most  exposed,  as  those  of  the  nose,  then  the  mucous 
membrane  of  the  mouth.  Spontaneous  hemorrhages  may  also  occur  from  the 
mucous  membrane  of  the  urinary  organs  and  from  the  female  sexual  organs, 
also  from  the  lungs,  the  stomach  and  the  intestines.  The  hemorrhages  from 
the  skin  are  most  likely  to  occur  in  cicatrices,  or  from  cuts  or  ulcers,  and  the 
hemorrhage  then  takes  place  during  a  period  in  which  the  rupture  of  con- 
tinuity is  beginning  to  heal.  Spontaneous  mucous  membrane  hemorrhages 
are  occasionally  combined  with  those  of  the  surface  of  the  skin.  In  subcu- 
taneous effusions  of  blood  which  embrace  a  wide  area  occasionally  suppuration 
is  noted,  leading  to  gangrene  of  the  skin  and  external  perforation,  after  which 
a  slough  consisting  of  brownish  and  gangrenous  shreds  is  discharged.  The 
blood  in  the  subcutaneous  hematomata  remains  fluid  for  a  long  time  similar 
to  the  condition  in  arthritic  hemorrhages,  and  the  careless  opening  of  such 
foci  may  lead  to  uncontrollable  and  fatal  hemorrhages;  the  latter  may  even 
occur  when  these  hematomata  rupture  spontaneously. 

Interstitial  spontaneous  hemorrhages  occur  most  frequently  in  the  scalp 
and  in  the  face,  next  in  the  scrotum,  more  rarely  in  the  extremities,  and  least 
frequently  upon  the  trunk.  Often  the  tips  of  the  fingers  are  implicated,  and 
the  blood  may  exude  or  spurt  from  them  as  from  a  sponge  dipped  in  blood. 
Although  these  hemorrhages  appear  spontaneously,  i.e.,  without  visible  ex- 
ternal cause,  it  may  be  regarded  as  certain  that  they,  as  well  as  the  "  trau- 
matic "  ones  now  to  be  described,  are  due  to  very  slight,  scarcely  determinable, 
mechanical  insults.  Intraparenchymatous  hemorrhages  of  internal  organs, 
perhaps  with  the  exception  of  the  kidneys,  very  rarely  occur  in  areas  which 
are  protected  from  external  influence,  a  circumstance  which,  according  to 
Strümpell,  forms  an  essential  difference  between  hemophilia  and  the  acquired 
hemorrhagic  diathesis. 

Superficial  traumatic  hemorrhages  may  take  place  in  any  superficially  lying 
part  of  the  body,  in  all  areas  of  the  skin,  and  upon  the  superficially  situated 
mucous  membranes,  as  well  as  upon  those  mucous  membranes  whose  secretions 
are  discharged  per  vias  naturales.  To  these  must  be  added  the  serous  mem- 
branes of  the  thoracic  and  abdominal  cavities.  Hemorrhages  from  the  surface 
and  from  the  mucous  membranes  which  are  susceptible  to  ordinary  inspect  ion 
may  be  produced  by  a  laceration,  a  puncture,  a  bite  or  other  wound,  also  by 
a  blow,  a  fall,  and  by  surgical  operations.  It  is  to  be  remarked  in  this 
connection  that  accidental  ruptures  of  continuity,  particularly  those  of  an 
irregular  form,  cause  hemorrhage  in  hemophiliacs  much  more  readily  than 
those  produced  by  design,  as  in  surgical  operations.  Cutaneous  areas  with 
ulcerating  processes  and  cicatrices  are  loci  minoris  resistentia.  Of  the  various 
regions  of  the  body,  the  head  is  the  one  in  which  the  hemorrhage  of  hemo- 


HEMOPHILIA  437 

philiacs  assumes  an  exceptionally  severe  character.  Probably  the  nio=t  copi- 
ous hemorrhages  occur  after  the  extraction  of  teeth.  In  one  case  reported. 
the  rupture  of  the  hymen  was  followed  by  lethal  hemorrhage.  It  is  a  peculiar 
fact  that  small  wounds  in  hemophiliacs  bleed  in  proportion  much  more  pro- 
fusely than  larger  wound-.  Fordyce  controlled  a  hemorrhage  by  enlarging 
the  wound  with  a  knife.  This  method  appears  to  be  the  best  in  the  case 
of  lacerated  wounds  which  bleed  profusely.  Traumatic  surface  hemorrhages 
usually  occur  from  only  one  isolated  point.    The  blood  exudes  from  the  wound 

rom  a  sponge  -aturated  with  blood;  nowhere  can  a  spurting  artery  be 
found. 

Interstitial  hemorrhages  after  trauma  occur  particularly  in  the  skin  and 
the  subcutaneous  connective  tissue.  They  follow  the  slightest  external  cans  s. 
ish,  a  blow  in  sport,  or  prolonged  pressure  as  in  sitting  or  lying,  may 
produce  interstitial  hemorrhages.  Blood  tumors  are  formed  (hematomata ). 
Those  areas  on  the  surface  of  the  body  are  most  liable  to  interstitial  hemor- 
rhages, which,  from  the  habit  of  life,  are  most  exposed  to  pressure,  the  but- 
tocks and  the  upper  posterior  parts  of  the  leg.  as  well  as  the  back. 

Diffuse  hematomata  are  found  especially  in  the  soft  parts  of  the  arms  and 
thighs,  as  well  as  occasionally  in  the  sheath  of  the  psoas  muscle.  They  occa- 
sionally resemble  an  abscess,  with  tense,  glistening,  hyperemic  skin,  and  are 
very  painful.  The  subcutaneous  effusions  of  blood  may  extend  over  a  wide 
area;  upon  suppuration,  gangrene  of  the  skin  and  external  rupture  have 

rved  as  in  spontaneous  hemorrhages;  a  chocolate-colored  mass  intermit;, 
with  gangrenous  shreds  is  then  discharged. 

The  other  most  important  symptom  of  tL  ■     is  the  great  difficulty 

with  which  the  hemorrhage  is  controlled.  This  forms  the  chief  danger  of 
the  malady,  and  is  the  reason  why  bleeders  very  rarely  attain  old  aire.  The 
open,  hemophilic  bleeding  reveals  perfectly  the  characteristics  of  parenchyma- 
tous hemorrhage.  From  the  entire  surface  which  has  been  exposed  by  the 
traumatic  rupture  of  continuity,  the  blood  oozes  continuously  for  many  hours. 
Even  by  the  most  careful  observation  it  is  impossible  to  find  a  spurting 
vessel. 

How  long  the  hemorrhage  may  continue  in  the  individual  case  cant 
foretold.  It  is  quite  uncertain,  but  the  excessive  loss  of  blood  in  its 
favorably  in  controlling  the  hemorrhage.  The  bleeding  hemophiliac  is  at- 
tacked  by  syncope;  shortly  afterward  the  hemorrhage  -  3.  Frequently, 
however,  it  Lasts  for  so  1< «iilt  a  time  as  to  bring  about  a  fatal  issue.  During  the 
hemorrhage,  frequently  there  is  at  first  in  -  cardiac  activity;  later,  in 
consequence  of  increasing  anemia  the  puis«  -  small,  sometimes  imper- 

ceptible, tin-  patient  is  pale  and  feeble;  in  very  severe  cases  there  are  delus 
convulsions  and  delirium. 

The  exuding  blood  at  firel  appears  normal:  if.  however,  the  hemorrhage 
i-  long  continued,  it  constantly  becomes  lighter  and  of  a  watery,  har- 

acter,  owing  to  the  increasing  anemia.  Chemical  and  microscopical  in- 
gations  of  the  blood  have  uoi  given  uoteworthy  results.  There  is  do  evid 
to  support  [mmermann's  theory  thai  the  hemorrhages  are  due  to  a  plethora. 

The  interstitial  hemorrhages  under  the  surface  of  the  skin  form  b 


438  THE  HEMORRHAGIC  DIATHESES 

tumors  (hematomata),  which,  in  accordance  with  the  transformation  of  the 
hemoglobin,  may  show  the  well  known  changes  of  color  observed  in  all  depos- 
its of  blood.  Now  and  then  a  hematoma  of  this  kind  suppurates  and  ruptures. 
Such  hemorrhages  damage  the  nutrition  and  constitution  of  the  patient  all 
the  more  as  they  lead  to  certain  complications  which  will  be  more  minutely 
described  later.  Moreover,  the  knowledge  that  he  is  affected  with  such  a 
disease  as  hemophilia  severely  disturbs  the  psychical  condition  and  the  nervous 
system  of  the  patient. 

Among  the  characteristic  complications  of  hemophilia  the  tendency  to 
"  rheumatic "  muscular  and  arthritic  disease  occupies  the  most  important 
place,  partly  for  the  reason  that  we  recognize  in  this  a  close  analogy  to  the 
hemorrhagic  diathesis  in  general.  The  arthropatlties  which  may  appear  in 
any  of  the  joints  are  the  most  familiar  complications  of  this  affection;  first, 
on  account  of  their  frequency,  and  secondly,  because  their  recognition,  partly 
by  means  of  the  Köntgen  rays,  and  partly  by  local  surgical  treatment  which 
frequently  permits  direct  inspection  of  the  open  joints,  has  led  to  more  accu- 
rate knowledge  of  them.  They  occur  spontaneously  as  well  as  in  consequence 
of  trauma  which  may  be  extremely  slight,  for  they  occur  even  in  bedridden 
patients  who  can  scarcely  move.  Frequently  they  are  of  undoubted  "  rheu- 
matic "  nature,  for  the  tendency  of  hemophiliacs  to  be  affected  by  "  rheumatic 
irritation "  is  very  great.  The  peculiar  relation  which  exists  between  the 
hemorrhagic  diathesis  and  diseases  of  the  joints  will  be  more  closely  consid- 
ered in  the  next  chapter.  In  hemophilic  arthropathies  the  knee-  and  elbow- 
joints  are  particularly  often  implicated.  The  disease  begins  with  pain  and 
swelling  which  may  lead  to  stiffness  and  a  position  of  flexion,  as  in  subacute 
arthritic  inflammation,  or  with  a  tumor  albus.  The  diagnosis  is  not  always 
easy,  and  sometimes  can  be  made  only  by  noting  the  other  hemophilic  phenom- 
ena which  have  preceded  the  joint  disease.  The  latter  occurs  most  frequently 
in  isolated  attacks  which  may  be  recognized  by  the  pain  and  swelling  of 
certain  joints  as  well  as  by  fever,  exactly  as  in  the  case  of  polyarthritis 
rheumatica.  The  course  of  the  disease  is  naturally  a  very  chronic  one. 
In  the  majority  of  cases  it  is  young  males  who  are  affected  by  hemophilic 
arthritis. 

F.  König  divides  the  arthritic  affection  of  bleeders  into  three  stages :  First, 
the  stage  of  initial  hemorrhage,  the  hemarthros  of  bleeders.  With  proper  care 
the  hemarthros  may  heal  and  the  disease  may  terminate  in  this  stage.  If  this 
is  not  the  case  the  blood  acts  as  an  irritant,  more  blood  is  added,  and  a  peculiar 
form  of  inflammation  develops  (second  stage)  which  shows  itself  as  a  pan- 
arthritis, and  which  in  the  pathology  as  well  as  in  its  clinical  symptoms  shows 
great  similarity  to  tuberculosis  of  the  joints.  This  stage  is  to  be  designated 
as  the  inflammatory,  the  hemophilic  tumor  albus.  The  third  stage  is  the 
retrogressive,  the  stage  which  leads  to  permanent  deformity  of  the  joints,  the 
contracted  bleeder  joint  with  dissolution  of  the  joint  cavity,  adhesions,  and 
•  lisplacements  of  the  arthritic  surfaces,  and  finally  ankylosis  and  deformity 
of  the  joint  ends. 

König's  division  appears  to  have  found  general  acceptance  among  surgeons. 
The  first  stage  is  not  to  be  viewed  as  though  we  were  dealing  with  but  a  single 


HEMOPHILIA  439 

hemorrhage.  On  the  contrary,  the  most  characteristic  feature  of  this  stage  is 
the  fact  that  one  or  more  effusions  of  blood  are  promptly  absorbed  without 
any  external  derangement  or  even  diminution  of  function  remaining  which 
can  be  recognized  by  disturbance  or  change  in  the  joints.  Gocht,  in  Hoffa's 
Clinic,  observed  in  different  hemophilic  youths  quite  a  number  of  more  or  less 
severe  arthritic  hemorrhages,  either  without  a  determinable  trauma  or  as  its 
direct  consequence.  The  knee-joint,  which  he  mentions  as  the  one  most  fre- 
quently affected,  at  times  appeared  to  be  enormously  thickened  by  a  large 
effusion  which  occurred  very  suddenly,  sometimes  in  from  five  to  ten  minutes. 
The  joint  was  sometimes  in  slight  flexion,  at  other  times  also  in  extension; 
sometimes  there  was  pain,  at  other  times  none.  Sometimes  the  joint  was  fixed 
and  immovable,  again  the  function  was  not  at  all  disturbed.  A  patient  in 
Hoffa's  Clinic  had  more  than  45  severe  hemorrhages  in  the  right  knee-joint 
without  suffering  the  slightest  inconvenience  in  the  use  and  function  of  the 
joint.  The  left  knee-joint  which  was  contracted  had  sustained  about  -±0  hemor- 
rhages; the  first  ;)(.»  gave  rise  to  no  injury;  only  the  last  effusion  of  blood 
led  to  permanent  contracture.  If  the  effusion  is  not  absorbed,  the  swelling 
in  the  joint  remains  and  is  not  amenable  to  treatment,  as,  for  instance,  was 
the  case  in  this  last  mentioned  knee-joint  which  led  to  contraction.  Pains 
appear,  and  the  function  is  much  interfered  with.  According  to  König  we 
are  then  dealing  with  that  peculiar  form  of  inflammation  (second  stage) 
which,  as  well  in  its  pathology  as  in  the  clinical  symptoms,  closely  resembles 
tuberculosis  of  the  joint,  and  which  was  called  by  this  author  hydrops  lubcr- 
rulnsiis  /ihrinosus.  The  picture  of  the  latter  disease  is  simulated  even  to  the 
most  minute  detail.  In  such  cases  the  contents  of  the  joint  are  hemorrhagico- 
serous  or  serous  with  a  brownish  color.  The  synovial  intima  shows  swelling 
and  brownish  discoloration,  and  a  large  number  of  fluctuating,  brownish, 
discolored,  synovial  villi.  The  coagula  of  blood  in  some  areas  may  attain 
enormous  thickness.  The  cartilage  loses  its  white  color  and  its  Luster,  and 
shows  a  brownish  discoloration;  it  is  partially  softened  because  its  upper 
layer  has  been  lost.  It  also  shows  defects  and  imevenness  in  its  surface  on 
aecount  of  an  irregular  loss  of  substance.  The  investigation  of  such  joints 
with  the  Röntgen  rays  has  been  described  by  Gochi  as  follows:  We  recognize 
that  the  lower  end  of  the  femur  upon  the  deformed  side,  in  contract  to  the 
other  side,  is  decidedly  smaller.  The  difference  amounts  to  more  than  1  cm. 
The  hones  upon  the  diseased  side  are  atrophic  and  too  permeable  to  the 
Röntgen  rays,  a-  may  he  recognized   from  the  lighter  color  in  the  skiagram. 

The  epiphysial  line-  upon  the  femur  and  tibia  do  not  show   the  normal  rounded 

edge,  hut  they  are  irregular,  serrated,  with  double  contours.  Upon  the  epiph- 
ysis of  the  femur  anomalous  indentations  are  shown.  While  upon  the  normal 
sidi  an  open  space  denote-  the  presence  of  normal  cartilage,  and  the  osseous 
ends  of  the  femur  and  tibia  presenl  their  norma]  forms,  the  conditions  upon 
the  diseased  side  are  quite  different:  Corresponding  to  the  loss  of  cartilage. 
a  decidedly  decreased  joint  space  is  found.  The  end-  of  the  hone-  appear 
completely  changed;  the  end   <d'  the   femur   i-   serrated   and    irregular;   the 

indentation  normally  between  the  condyles  i-  lost,  and  the  intercondylar  emi- 
nence of  the  tibia  i-  irregular  and  extended.    The  recent  losses  in  structure 


440  THE  HEMORRHAGIC  DIATHESES 

and  the  recent  deposits  fit  each  other.  The  capsular  shadows  upon  the  inner 
side  of  the  contracted  knee-joint  are  darker  than  upon  the  normal  side. 

In  the  case  of  an  older  boy,  in  whom  remarkable  changes  had  taken  place, 
the  cartilage  space  in  the  joint  had  disappeared  entirely,  the  tibia  was  markedly 
dislocated  outwardly.  Between  the  bones  adhesions  could  be  seen.  The  rela- 
tions of  the  capsule  could  not  be  judged  from  the  picture,  for  at  the  time  the 
plate  was  made  an  enormous  effusion  of  blood  had  occurred  in  the  joint, 
which  was  revealed  in  the  picture  as  an  oviform  shadow  the  size  of  a  hand. 

In  the  diagnosis  of  bleeder  affections  of  the  joint,  in  accordance  with 
König's  views,  Gocht  differentiates  three  groups  as  follows: 

1.  Individuals  who  are  well-known  bleeders, 

2.  Those  who  have  not  been  known  to  be  bleeders,  but  who  present  charac- 
teristic symptoms  of , hemophilia  besides  the  arthritic  affection, 

3.  Those  in  whom  neither  the  history  nor  any  prominent  symptom  indi- 
cates the  general  affection. 

If  there  is  no  history  of  hemophilia,  such  as  preceding  severe  hemorrhages, 
the  very  rapid  development  of  an  effusion  into  the  joints  without  noteworthy 
trauma  and  an  accurate  examination  may  lead  to  the  proper  diagnosis.  The 
pains  are  often  out  of  all  proportion  to  the  severity  of  the  case,  and  the 
function  of  the  implicated  joint  may  be  scarcely  impaired.  This  is  especially 
the  case  if  the  patient  is  seen  in  the  first  stage  of  the  disease.  If,  on  the 
other  hand,  a  joint  is  found  in  the  stage  of  inflammation,  the  diagnosis  be- 
comes more  difficult,  as  the  clinical  picture  of  the  bleeder  joint  is  identical 
with  that  of  hydrops  fibrinosus  tuberculosus.  The  difficulty  lies  in  the  fact 
that  the  investigator  rarely  considers  the  possibility  that  he  is  dealing  with 
the  diseased  joint  of  a  bleeder.  For,  if  hemophilia  is  considered  at  all,  an 
error  in  diagnosis  is  virtually  excluded.  The  following  phenomena  point  to 
a  hemophilic  joint:  subacute  hemorrhages  and  scleroses  about  the  joints; 
freshly  developed  effusions  into  the  joints,  or  hemorrhages  under  the  skin 
into  the  muscles,  etc. ;  last,  and  above  all,  the  signs  of  previous  disease  in  other 
joints.  König  also  declares  that  in  hemophilia  the  patients  are  generally 
youthful  males  with  a  conspicuous  pallor  of  the  face.  This  latter  symptom 
Gocht  quite  properly  denies,  for,  in  the  first  place,  bleeders  may  show  a 
healthy  color  of  the  face,  and,  on  the  other  hand,  patients  with  tumor  albus 
are  for  the  most  part  extremely  pale,  though  of  course  abscess  and  formation 
of  fistula,  which  are  common  with  tumor  albus,  are  exceedingly  rare  in 
hemophiliacs.  In  doubtful  cases  one  or  more  injections  of  tuberculin  may 
be  used  for  diagnostic  purposes. 

From  what  has  been  said,  it  is  evident  that  the  recognition  of  a  bleeder's 
joint  may  sometimes  be  very  easy,  at  other  times  difficult  but  still  possible, 
occasionally  impossible. 

Gocht  agrees  with  Linser  that  those  bleeders  who  do  not  suffer  from  disease 
of  the  joints  are  exceptions.  Almost  invariably  the  arthritic  affection  is 
localized  in  one  knee-joint.  This  may  be  due  to  the  fact  that  the  knee-joint 
is  most  exposed  to  injury  on  account  of  the  great  extent  of  its  surface  and  its 
exposed  position.  The  first  hemorrhages,  as  well  as  the  great  majority  of  the 
later  ones,  are  due  to  external  causes.     That  children  are  not  attacked  by 


HEMOPHILIA  441 

hemorrhages  of  the  joints  prior  to  learning  to  walk  is  explained  by  the  absence 
of  trauma.  If,  however,  during  the  period  in  which  they  learn  to  walk,  the 
joints  are  brought  into  use  as  well  as  the  muscles,  the  time  for  hemorrhage 
of  the  joint  has  come,  for  the  physiologic  function  of  the  joint  is  to  be  looked 
upon  as  a  -cries  of  traumatic  influences!  Quite  often  surgeons  note  the 
appearance  of  arthritic  hemorrhages  of  the  most  severe  type  even  though  the 
patient  remains  in  bed,  and  is  apparently  not  exposed  to  the  slightest  external 
injury.  In  such  instances  the  joints  affected  are  those  that  have  been  repeat- 
edly the  seat  of  effusions  of  blood.  Probably  because  of  the  hyperplasia  of 
the  synovial  villi,  in  consequence  of  changes  in  the  surface  of  the  cartilage, 
and  on  account  of  the  great  predisposition  to  hemorrhages,  any  slight  motion 
may  cause  a  laceration  of  such  synovial  villi,  and  so  give  rise  to  severe 
hemorrhages. 

The  question  whether  the  predisposition  to  arthritic  hemorrhages  decreases 
with  time  must  generally  be  answered  in  the  affirmative.  For.  as  we  have 
already  pointed  out,  according  to  the  general  views  of  hemophilia,  the  tendency 
to  bleed  declines  in  later  life,  and  disappears  entirely  in  the  aged.  We  must 
likewise  assume  that  a  predisposition  to  arthritic  hemorrhages  gradually  de- 
creases, especially  since  the  children  become  less  active  as  the}'  grow  up  and 
greater  care  is  taken  to  prevent  injuries.  Another  point  which  Gocht  also 
considers  in  his  observations  is,  whether  the  joints  finally,  in  consequence  of 
pathologico-anatomical  changes,  lose  their  tendency  to  hemorrhage.  If  a  joint 
enters  the  third  stage,  the  retrogressive,  if  destruction  of  the  joint  cavity  has 
developed,  if  the  former  hyperplastic  villi  have  contracted,  or  if  adhesions 
in  the  connective  tissue  of  a  cartilaginous  or  osseous  character  have  occurred. 
hemorrhages  will  be  much  rarer,  in  the  first  place,  for  anatomical  reasons, 
and,  secondly,  because  irritation  due  to  motion  is  no  Longer  present. 

Still  another  factor  musl  be  considered — the  variation  in  the  individual 
predisposition.  It',  as  we  have  seen,  one  hemophilic  patient  is  capable  of  with- 
standing more  than  lö  severe  arthritic  hemorrhages  without  apparently  suffer- 
ing in  function,  while  another  readily  develops  a  panarthritis,  it  follow-  that 
the  power  to  absorb  the  effusion  of  blood  in  the  joints  also  varies  greatly  in 
diU'ereni  patients.  The  question  of  the  coagulability  of  the  blood  in  the  hemo- 
philiac, which  is  still  open  und  undecided,  need  not  enter  into  this  discussion. 

According  to  Gayel  and  Th.  Hirsch,  the  clinical  phenomena  of  the  arthritic 
affections  of  the  hemophiliac  resemble  especially  an  acute  or  subacute  arthri- 
tis (on  account  of  pain  and  swelling,  fever,  Btiffness,  and  the  flexed  position). 
On  the  side  of  pathogenesis,  these  authors  believe  that,  besides  hemorrhagic 
processes,  we  cannot  deny  a  rheumatic  influence  in  the  joint  affections. 

Of  other  complication-,  the  neuropathic  predisposition  is  to  be  mentioned, 
which  in  Borne  patient-,  chiefly  women,  presents  itself  in  manifold  ways. 
Here  the  hereditär)  neuropathic  predisposition  is  especially  prominent.  Neu- 
ralgia ie  a  relatively  frequenl  occurrence  in  bleeders,  and  occasionally  neuritis 

has  al-o  I n  noticed.     In  Borne  cases  a  long-continued   fever  without   local 

changes  has  I n  observed.  Finally,  I  musl  mention  the  appearance  of  cir- 
cumscribed, hard,  painful  infiltrations  into  the  -kin  and  the  subcutaneous 
connective  tissue,  above  which  the  skin   remain-  unchanged   in  color;  later 


442  THE  HEMORRHAGIC  DIATHESES 

these  may  undergo  the  characteristic  changes  which  occur  in  the  extravasa- 
tions, or  they  may  disappear  without  these  changes. 

LOCAL  HEMORRHAGES  UPON  A  HEMOPHILIC  BASIS 

In  the  last  decade  a  number  of  cases  have  been  published  in  which  the 
common  characteristic  was  a  more  or  less  profuse  hemorrhage  from  a  kidney, 
the  absolute  integrity  of  the  organ  being  determined  either  by  clinical  observa- 
tion or  by  operation.  In  these  important  cases  the  question  arises:  What 
factor  is  the  cause  of  the  hemorrhage?  Although  Lauenstein  published  his 
fundamental  case  in  the  year  1887,  and  a  large  number  of  similar  observations 
followed  (those  of  Sabatier,  Schede,  Anderson  and  Leguen  in  the  years  1889 
and  1890),  only  Senator's  article  ("Kegarding  Eenal  Hemophilia,"  1891)  can 
be  accorded  scientific,  authoritative  importance.  I  shall  therefore  give  a 
synopsis  of  the  case : 

A  girl,  aged  nineteen,  in  the  year  1887,  noted  blood  in  the  urine  immedi- 
ately after  menstruation.  The  examination  of  the  voided  hemorrhagic  urine 
at  that  time  showed,  a  large  amount  of  hemoglobin  although  no  red  blood- 
corpuscles.  After  the  lapse  of  two  years,  during  which  time  decided  debility 
and  periodic  cough  gave  rise  to  the  suspicion  of  tuberculosis,  the  hemorrhage 
recurred ;  this  time  it  was  more  profuse,  and  lasted  with  slight  intervals  more 
than  six  months.  The  analysis  of  the  urine  showed  actual  hematuria;  the 
blood  discharged  through  the  kidneys  differed  but  very  little  from  pure  un- 
mixed blood.  Toward  the  end  of  February,  1890,  Senator  determined  the 
following:  Patient  is  well  formed,  very  pale,  no  trace  of  emaciation.  The 
internal  organs  present  nothing  abnormal;  lungs  and  kidneys  apparently 
healthy.  Urination  painless,  perhaps  somewhat  more  frequent  than  normal, 
but  without  tenesmus.  The  urinary  sediment  consists  exclusively  of  erythro- 
cytes; crystals,  pus  and  other  pathologic  constituents  are  absent.  No  fever. 
The  examination  carried  out  under  an  anesthetic  shows  no  changes,  neither 
in  the  kidney  nor  in  the  bladder  nor  in  the  sexual  organs,  but  it  was  demon- 
strated by  means  of  the  cystoscope  that  the  blood  flowed  from  the  right  ureter. 
After  the  usual  causes  of  hemorrhage,  such  as  stone,  tumor  and  tuberculosis, 
had  been  excluded,  Senator  made  a  diagnosis  of  hemophilia  which  was  con- 
firmed by  the  history.  It  was  ascertained  that  the  patient  was  a  member  of 
a  family  in  which  hemorrhages  occurred  frequently.  Four  sisters,  and  a 
brother  aged  seventeen,  showed  great  tendency  to  epistaxis;  the  father,  who 
at  the  time  was  quite  healthy,  as  a  child  had  been  frequently  attacked  by 
nose  bleed  and  hemoptysis  without  showing  any  pulmonary  lesions.  Eleven 
brothers  and  sisters  of  the  father  suffer  or  have  suffered  from  epistaxis;  an 
uncle  of  the  patient,  who  for  a  long  time  suffered  from  epistaxis,  in  his 
twentieth  year  had  an  attack  lasting  twenty-four  hours,  after  which  purpura 
appeared  over  the  entire  body  and  hematemesis  occurred;  the  disease  ended 
fatally  after  fourteen  days.  A  second  uncle  is  the  father  of  two  children 
who  have  inherited  epistaxis  from  him.  The  mother  of  the  father,  up  to 
the  time  of  her  death,  menstruated  profusely.  Unquestionably,  therefore,  the 
patient  was  a  member  of  a  bleeder  family.    Although  no  symptoms  of  hemo- 


HEMOPHILIA  443 

philia  had  previously  appeared,  Senator  believes,  in  the  absence  of  other 
causes,  that  he  may  assume  a  hematuria  of  hemophilic  origin.  The  continued 
hemorrhage  resulted  in  a  severe  anemia  which  resisted  all  internal  remedies, 
and  for  this  reason  nephrectomy  was  proposed  and  performed.  The  organ 
was  laid  bare  and  removed,  although  apparently  unchanged.  The  further 
course  of  the  disease  was  very  favorable.  Upon  the  second  day  after  the 
operation  the  blood  disappeared  from  the  urine  and  never  recurred.  Four 
weeks  later  the  patient  left  the  hospital  entirely  well.  The  examination  of 
the  extirpated  kidney  showed  small  inflammatory  foci  and  extravasations; 
otherwise  'the  organ  was  absolutely  normal. 

I  shall  add  to  this  two  other  analogous  cases  observed  in  v.  Leyden's  clinic 
and  described  by  G.  Klemperer: 

1.  A  man.  aged  thirty-five,  admitted  to  the  clinic  on  the  15th  of  April, 
1893.  The  father  of  the  patient  died  of  enteric  fever,  the  mother  is  living 
and  since  earliest  childhood  has  suffered  from  frequent  subcutaneous  hemor- 
rhages and  marked  bleeding  even  after  insignificant  injuries.  A  brother  died 
of  hemorrhage  (hiring  an  amputation.  Another  brother  of  the  patient  is  also 
predisposed  to  hemorrhages.  The  patient  himself,  immediately  after  birth, 
had  a  severe  hemorrhage  from  the  umbilical  cord.  In  childhood  hemorrha 
frequently  occurred  from  the  nose  and  other  parts  of  the  body  after  insignifi- 
cant trauma.  From  his  third  year,  he  suffered  from  swelling  of  the  joints 
of  the  upper  and  lower  extremities.  As  a  rule  these  swellings  occurred  sud- 
denly without  cause,  usually  early  in  the  morning;  they  were  extremely  pain- 
ful, but  often  disappeared  on  the  same  evening;  complete  motility  of  the  limits, 
however,  did  not  return  until  some  months  after  the  attack.  At  fifteen  the 
patient  bad  a  fracture  of  the  thigh  and  severe  subcutaneous  hemorrhages  de- 
layed normal  recovery.  His  first  attack  of  hematuria  occurred  at  sixteen, 
accompanied  by  dull  pain  in  the  right  renal  region,  which  soon  became  colic- 
like; this  was  followed  by  nausea  and  vomiting.  The  urine  was  of  a  bloody 
ml  or  black  color.  This  condition  lasted  for  several  months,  the  hemorrhages 
recurring  at  intervals  of  from  six  months  to  two  years.  One  attack  of  hema- 
turia lasted  thirteen  weeks.  The  patient  did  not  -eck  professional  aid.  as 
he  believed  himself  to  he  a  bleeder,  and  looked  upon  the  hematuria  as  a  symp- 
tom of  the  genera]  affection.  During  the  attacks  he  remained  quiet,  and 
relieved  the  pain  by  Large  doses  of  morphin  which  had  firsl  been  used  at  the 
time  of  the  enlargement  of  the  joints.  The  patieiil  came  to  the  clinic  princi- 
pally b>r  the  treatment  of  his  morphinism.  He  is  pale,  nervous;  the  internal 
organs  are  normal.     Upon  the  fourth  day  after  admission  a  renal  hemorrhage 

occurred  which  lasted  for  two  weeks.  The  urine  contained  pure  blood.  The 
patient    «;i-  discharged  cured    upon   (he   15th  of   May,    l>>'.r-'>.      Toward   the  etui 

of  his  stay  in  the  hospital  two  hemorrhages  into  tin'  wrist-joints  occurred. 
Subsequently  this  happened  quite  frequently.  Op  to  March.  1896,  the  hema- 
turia had  not  recurred. 

2.  The  other  case  «ras  that  of  an  official  aged  twenty-sii  years,  the  history 
showing  hut   slight    hereditary    predisposition.     The   patient    himself   was   a 

bleeder.       From    the   age   of    -i\teeii.    aluio-t    e\  erv   year   attacks   of    hematuria 

occurred,  which  occasionally  were  repeated  BeveraJ  times  in  the  year,  and  lasted 


444  THE  HEMORRHAGIC  DIATHESES 

for  hours  or  weeks.  With  these  the  patient  had  insignificant  pain  in  the 
right  renal  region.  He  consulted  a  physician  only  when  a  hemorrhage  lasted 
longer  than  eight  days.  Upon  the  2d  of  November,  1895,  pain  occurred  in 
the  right  renal  region,  and  upon  the  9th  of  November  lie  voided  bloody  urine. 
Examination  showed  nothing  abnormal;  no  pathologic  constituents  except 
blood  were  found  in  the  urine.  In  spite  of  numerous  remedies  the  hemorrhage 
continued,  and  the  anemia  constantly  became  more  marked.  Upon  the  28th 
of  December  all  drugs  were  stopped,  and  hydrotherapy  was  begun.  The 
patient  had  a  bath  each  day  lasting  ten  minutes,  followed  by  affusions  to  the 
renal  region.  The  bath  was  begun  at  a  temperature  of  95°  F.,  the  water  being 
gradually  cooled  to  75.2°  F.  The  affusions  were  at  a  temperature  of  82.4°  F. 
to  60.8°  F.  Gradually  the  hemorrhages  became  slighter,  and  the  urine  finally 
cleared.    Upon  the  15th  of  January  the  patient  left  the  clinic  cured. 

A  fourth  case  is  published  by  S.  Grosglik :  "  Ueber  Blutungen  aus  anatom- 
isch unveränderten  Nieren"  (Sammlung  Min.  Vorträge,  Nr.  203).  An  army 
officer,  aged  thirty-six,  of  a  bleeder  family  on  both  paternal  and  maternal  sides. 
The  patient  was  of  healthy  appearance,  but  suffered  frequently  from  marked 
epistaxis  and  hemorrhage  from  the  rectum.  In  September  and  December, 
1896,  he  had  severe  hematuria  for  which  clinically  no  cause  could  be  assigned. 
As  the  patient's  history  was  unknown  at  that  time,  the  diagnosis  wavered  be- 
tween a  beginning  tumor  and  tuberculosis  of  the  kidney.  After  an  observa- 
tion of  six  months,  as  no  further  point  of  support  could  be  determined  for 
either  diagnosis,  and  after  the  patient  had  related  his  family  history,  Gros- 
glik made  the  diagnosis:  "Idiopathic  renal  hematuria  upon  a  hemophilic 
basis." 

In  other  cases  of  "  nephralgie  hematurique  "  in  which  the  hematuria  could 
not  be  assigned  to  a  hereditary  hemophilic  constitution,  it  has  been  assumed 
that  the  cases  were  due  to  vasomotor  or  traumatic  renal  hemorrhage  (i.  e., 
due  to  corporeal  over-exertion).  Accordingly,  varieties  of  hemophilic  vaso- 
motor and  traumatic  renal  hemorrhage  might  be  described  in  which  the  possi- 
bility of  other  causes  for  hemorrhages  than  an  anatomical  substratum  could 
not  be  excluded. 

In  regard  to  the  diagnosis,  if  there  is  no  enlargement  of  the  kidney,  and 
if  the  composition  of  the  urine  and  the  accompanying  symptoms  do  not  favor 
an  organic  affection,  the  following  facts  are  of  importance :  The  proof  of  a 
hereditary  hemophilic  predisposition,  a  preceding  exertion,  or  disturbances  of 
the  nervous  system  (hysteria,  neurasthenia,  etc.)  by  which  the  vasomotor 
center  for  the  kidney  might  be  implicated.  If  the  history  reveals  anything 
positive,  the  diagnosis  of  essential  hematuria  becomes  likely.  It  only  becomes 
certain,  however,  when,  after  prolonged  observation,  no  distinct  signs  of  ana- 
tomical change  have  appeared. 

The  treatment  of  hemophilic  renal  hemorrhage,  according  to  Grosglik, 
should  be  expectant.  If  the  course  of  the  affection  is  severe  internal  remedies 
are  powerless,  and  if  the  hemorrhage  threatens  to  prove  fatal  the  bleeding 
kidney  must  be  removed  as  soon  as  possible.  In  so-called  vasomotor  renal 
hemorrhages  the  diagnosis  should  be  immediately  confirmed  by  surgical  inter- 
ference, which  should  not  only  embrace  the  exposure  and  palpation  of  the 


HEMOPHILIA  445 

Organ  but  also  an  incision  into  the  kidney,  and  a  minute  investigation  of 
the  parenchyma.  If  the  incised  kidney  is  found  to  be  anatomically  unchanged, 
it  should  be  closed  by  suture  and  replaced.  If  this  procedure  affords  no  relief, 
a  secondary  nephrectomy  is  to  be  performed.  Primary  extirpation  is  not 
warranted  in  these  cases. 

How  little  data  the  exploration  of  an  incised  kidney  in  vivo  may  furnish. 
Zondek  recently  demonstrated  in  a  discussion  before  the  Society  of  Internal 
Medicine,  when  he  arrived  at  the  following  conclusions: 

1.  Even  in  a  kidney  laid  open  by  operation  the  presence  of  a  small  stone 
cannot  be  excluded  with  certainty. 

2.  Even  when  surgical  exploration  of  the  organ  gives  a  negative  result, 
inflammatory  changes  of  the  renal  tissue  may  be  due  to  a  stone  in  a  con- 
cealed calyx. 

3.  Complete  proof  of  the  diagnosis  of  angio-neurotic  hemorrhage  from  the 
kidnev  necessitatis  the  most  careful  investigation  of  the  entire  kidney  after 
it  has  been  removed  from  the  body,  and  also  of  the  ureter  down  to  its  point 
of  entrance  into  the  bladder. 

Harris  (Philadelphia  Medical  Journal.  March  19,  1898)  published  two 
cases  of  "essential"'  renal  hematuria.  In  one  of  the  patients  the  kidney  was 
exposed.     In  both  cases  the  hemorrhage  ceased. 

Harris  has  collected  16  similar  cases  from  literature.  The  majority  of  the 
patients  were  cured  by  simple  nephrotomy.  He  comes  to  the  following  con- 
clusions: 1.  Renal  hemorrhages  occur  in  which  none  of  the  usual  causes,  acute 
nephritis,  tuberculosis,  sepsis,  neoplasms,  malaria,  etc.,  are  present.  ".'.  The 
pathological  changes  arising  in  the  kidney  are  unknown  to  us.  3.  These  hema- 
turias are  not  controlled  by  ordinary  styptics.  4.  If  tonics,  cold  baths,  etc., 
are  without  effect,  nephrotomy  must  be  performed.  5.  Primary  nephrectomy 
is  in  no  wise  indicated. 

J.  Israel  writes  on  the  curative  influence  of  renal  incision  in  cases  of  uni- 
lateral colic  and  unilateral  renal  hemorrhages  in  the  obscure  pathologic  condi- 
tion which  up  to  the  present  has  been  called  nephralgie,nephralgie  hemarurique, 
renal  hematuria  without  known  Lesions,  essential  or  angio-neurotic  renal  hemor- 
rhage, all  of  which, according  to  his  investigations, most  frequently  depend  upon 
chronic  inflammatory  change-  of  the  kidnev.  dp  to  the  year  1 898  he  had  oper- 
ated upon  1  i  cases  of  this  kind.  Five  kidneys  were  examined  microscopically, 
and  four  of  these  showed  different  forms  of  nephritis.  In  eight  of  the  remain- 
ing nine  patients,  microscopic  investigation  of  the  kidneys  showed  organic 
changes.  Of  the  fourteen  cases  treated  by  nephrotomy  three  died,  of  whom 
two  had  severe  bilateral  uephritis  ;  sis  were  completely  and'permanently  cured  ; 
three  after  apparent  recovery  Buffered  from  mild  relapses  of  varying  duration; 
in  two  patient-  the  operation  was  designated  as  useless. 

l-rael  has  summed  up  the  important  knowledge  obtained  from  these  obser- 
vations in  the  following:  1.  There  are  cases  of  unilateral  uephritis.  2.  There 
are  cases  of  renal  colic  due  to  uephritis  which  may  completely  simulate  colic 
from  calculi.  :'».  There  arc  cases  of  bilateral  nephritis  which  produce  only 
unilateral  colic.  I.  There  are  cases  of  severe  nephritis  with  absence  of  albu- 
min in  the  urine  and  absence  of  casts.     5.  The  mine  may  he  free  from  albumin 


446  THE  HEMORRHAGIC  DIATHESES 

in  spite  of  a  profusion  of  hyaline,  granular  and  epithelial  casts.1  6.  There 
are  cases  of  nephritis  with  paroxysmal,  profuse  hemorrhages.  7.  Nephritic 
hemorrhages  may  occur  and  run  their  course  with  or  without  colic ;  the  hemor- 
rhage is  not  the  cause  of  the  colic.  Both  phenomena  are  the  results  of  renal 
congestion.  8.  A  great  number  of  pathologic  conditions  designated  up  to 
now  as  nephralgie  hematurique  are  to  be  referred  to  nephritic  processes.  9. 
Incision  into  the  kidney  in  many  cases  influences  the  nephritic  process  and 
its  symptoms  favorably. — In  a  lecture,  "  Hemorrhage  from  a  Normal  or  Appar- 
ently Normal  Kidney,"  Naunyn  in  the  main  agrees  with  Israel  that  interstitial 
nephritis  is  the  most  frequent  cause  of  this  form  of  renal  hemorrhage. 

Pousson  in  two  cases  of  apparently  spontaneous  renal  hematuria  extirpated 
the  affected  kidney.  The  microscopic  examination  of  the  congested  kidney 
revealed  inflammatory  foci  in  the  renal  cortex  without  other  abnormalities. 
Poirier  and  Picque  advise  in  such  cases  only  the  operation  of  nephrotomy,  as 
frequently  the  other  kidney  also  presents  signs  of  chronic  nephritis.  In  con- 
trast to  this  Eegnier  believes  that  in  such  cases  we  are  invariably  dealing  with 
a  beginning  renal  tuberculosis  ( ?)  ;  he  therefore  strongly  advises  early 
nephrectomy. 

Hofbauer  (MUM.  a.  d.  Grenzgeb.  d,  Med.  u.  Chir.,  1899,  V,  3)  describes 
a  case  of  essential  unilateral  hematuria  in  a  girl  aged  thirteen:  It  was  espe- 
cially difficult  to  determine  in  this  case  the  etiology  of  the  hematuria  which 
had  persisted  for  two  years.  It  had  appeared  without  an  assignable  cause,  and, 
in  spite  of  this  great  duration,  had  produced  no  sequela?  with  the  exception  of 
anemia  and  its  consequences.  The  examination  of  the  urine  revealed  no 
pathological  constituents  except  an  admixture  of  blood.  .  Upon  cystoscopy  the 
urinary  bladder  was  found  normal ;  the  blood  was  seen  to  exude  from  the  left 
ureter  while  from  the  right  ureter  clear  urine  was  being  excreted.  No  signs 
upon  palpation.  An  exact  clinical  diagnosis  was  not  made.  On  account  of 
marked  loss  of  blood  there  was  an  exploratory  incision  only ;  this  did  not  fur- 
nish the  hoped-for,  absolute  certainty.  On  exposure,  the  kidney  was  found  to 
be  normal  in  size,  and  palpation  revealed  no  pathologic  changes. 

When,  to  facilitate  more  exact  inspection,  the  kidney  was  drawn  forward, 
a  laceration  of  one  of  the  larger  vessels  made  extirpation  necessary.  The 
hemorrhage  ceased.  Recovery  followed.  Macroscopically,  the  kidney,  the 
renal  pelvis,  and  the  ureter  were  perfectly  normal.  Microscopical  investiga- 
tion of  the  extirpated  organ  revealed  a  chronic  glomerular  nephritis.  In  this 
case  the  diuresis  following  the  nephrectomy  was  very  interesting.  The  amount 
of  urine  a  few  days  after  the  operation  not  only  equalled  the  former  amount 
but  decidedly  exceeded  it. 

In  1891  Senator,  in  his  case  of  renal  hemophilia  (Berliner  Jclin.  Woch- 
cii sehr..  1891,  Nr.  1),* tested  the  activity  of  the  remaining  left  kidney.  For 
this  purpose  he  examined  the  urine  daily  for  four  weeks  from  the  second  day 
after  nephrectomy,  in  regard  to  amount,  specific  gravity,  and  its  contents  of 

i  I  should  likr-  to  remark  in  this  connection  that  upon  the  occasion  of  the  Tenth 
Congress  of  Internal  Medicine  in  1891,  when  I  demonstrated  the  centrifuge  in  Wiesbaden 
for  the  first  time,  I  called  attention  to  the  fact  that  "casts  occur  quite  frequently  in 
urine  free  from  albumin,  and  can  scarcely  be  looked  upon  as  pathological." 


HEMOPHILIA  447 

nitrogen.  The  reaction  was  always  acid.  With  the  exception  of  the  first 
day  upon  which  the  urine  still  contained  some  blood,  and  upon  the  succeeding 
day  when  a  small  amount  of  albumin  was  present,  abnormal  constituents  were 
never  noted.  The  examination  for  nitrogen  was  conducted  according  to  the 
well-known  process  of  Kjeldahl,  and  several  times  urea  was  estimated  accord- 
ing to  Pflüger  \s  modification  of  Liehig's  method.  It  was  shown  from  the 
table,  published  in  Senator's  report  of  his  case,  that  immediately  after  the 
operation  the  remaining  left  kidney  performed  all  the  work  of  both  kidneys, 
perhaps  at  first  functionating  even  a  little  more,  for  a  daily  excretion  of 
nitrogen  of  over  IG  grams  (such  as  was  seen  in  this  case)  is  the  normal  for 
an  adult  person  with  a  plentiful  supply  of  food,  and  for  a  young  girl  in  such 
a  condition  (lessened  amount  of  food  after  the  operation)  is  a  decided  and 
abnormal  increase. 

Floderu8  in  Lennander's  Clinic  observed  a  case  of  renal  hematuria  with 
macroscopic-ally  unchanged  kidneys.  lie  examined  microscopically  the  kid- 
nev  extirpated  by  Lennander,  and  demonstrated  a  disseminated  sclerotic 
glomerulitis  with  advancing  sclerosis  in  the  adjacent  connective  tissue,  also 
fatty  degeneration  and  atrophy  of  the  epithelium.  In  consequence  of  this 
finding  Floderus  studied  minutely  the  previously  published  cases  of  so-called 
essential  renal  hemorrhage.  He  divides  these  cases  into  the  five  following 
groups : 

1.  Renal  hemorrhage  in  hemophilia. 

2.  Renal  hemorrhage  due  to  vasomotor  disturbance. 

3.  Hematuria  from  mechanical  causes. 

4.  Hemorrhage  from  kidneys  which  are  the  seat  of  nephritic  processes. 

5.  Imperfectly  described  cases  of  essential  renal  hemorrhage. 

After  these  literary  deductions  Floderus  enter-  upon  a  discussion  of  most 
of  tin'  cases  published,  minute  reports  of  which  are  entirely  lacking.  For 
this  reason  the  last  group  must  include  the  majority  of  the  cases  assigned  to 
the  four  other  groups,  Hi-  criticism  of  the  cases  described  in  literature  per- 
mits tli''  assumption  that  in  scarcely  a  single  instance  was  the  bleeding  kidney 
shown  to  he  intact  histologically. 

In  a  woman  aged  forty-five,  who  for  two  years  and  six  month-  suffered 
from  a  left-sided  renal  hematuria,  de  Keersmaecker  performed  nephrectomy. 
The  kidney  revealed  interstitial  and  parenchymatous  Inflammatory  nephritis 
(with  hemorrhage). 

Rovsing  has  written  a  long  article  regarding  unilateral  hematuria  of  ques- 
tionable origin  and  its  treatment  by  nephrectomy. 

Before  making  the  diagnosis,  "hemorrhage  from  normal  kidneys"  we 
musl  determine  by  all  method-  at  our  command:  1.  That  the  hemorrhage 
actually  originates  from  the  kidney;  2.  That  all  pathologico-anatomical 
changes  which  may  1»'  assumed  to  he  the  cause  of  renal  hemorrhage  are  abso- 
lutely excluded.  The  cases  published  may  he  divided  into  two  groups:  1. 
The  cases  treated  exclusively  by  medication;  2.  The  cases  in  which  the  kidney 
was  directly  palpated  by  operation,  was  incised,  or  was  removed.  Only  the 
last-named  <-a-e-.  of  uhieh  Rovsing  collected  report-  t>(  l."..  are  of  particular 
importance.     In  all  of  these  observations  the  authors  unanimously  -(ate  that 


448  THE  HEMORRHAGIC  DIATHESES 

they  were  unable  to  find  any  material  or  assignable  cause  for  the  hemorrhage; 
while,  from  the  circumstance  that  the  hemorrhage  ceased  after  operative  in- 
terference, whether  by  a  simple  exploration,  a  nephrotomy  or  a  nephrectomy, 
proof  was  given  that  the  hemorrhage  actually  arose  from  the  kidney  in  ques- 
tion. For  the  explanation  of  the  hemorrhage,  therefore,  the  assumption  of  a 
"  local  hemophilia  "  or  an  "'  angioneuro.-i-  "  is  in  these  cases  held  sufficient. 

If,  however,  the  published  clinical  histories .  are  critically  examined,  we 
arrive  at  the  conclusion  that,  as  a  matter  of  fact,  in  by  far  the  majority  of 
cases,  pathological  conditions  of  the  kidney  or  of  the  pelvis  of  the  kidney 
might  have  been  determined  which  would  explain  the  hemorrhage.  Finally, 
in  the  cases  in  which  the  kidney  has  been  found  apparently  normal,  the  pos- 
sibility was  not  considered  that  the  starting  point  of  the  hemorrhage  was  not 
in  the  kidney  substance  at  all.  but  in  the  pelvis  of  the  kidney,  or  in  the  ureter. 

Eovsing  communicates  four  personal  observations,  in  three  of  which  patho- 
logical changes  were  observed,  and  comes  to  the  following  conclusion-:  1. 
Many  of  the  published  cases  of  hemorrhage  of  nervous  origin  do  not  stand 
the  test  of  critical  analysis,  as  in  some  of  them  pathological  conditions  were 
actually  present  which  very  readily  explain  the  hemorrhage,  while  in  other 
-  s  the  investigation  was  not  thorough  enough  to  exclude  other  affections, 
not  only  those  of  the  kidney  but  also  those  of  the  bladder,  as  cystoscopy  was 
not  performed  to  determine  the  origin  of  the  hemorrhage  from  only  one  ureter. 
2.  There  is  no  doubt  that  in  a  number  of  cases  of  hematuria  from  normal 
kidneys,  dislocation  of  the  kidney  with  torsion  of  the  pedicle  or  kinking  of  the 
ureter  plays  an  important  role.  3.  The  first  case  mentioned  by  Eovsing  dem- 
onstrates the  fact,  unknown  till  then,  that  lacing  and  the  pressure  of  a  corset 
may  directly  cause  very  marked  disease  of  the  kidney.  4.  After  a  careful 
sifting  of  the  cases  a  few  -till  remain  in  which  decided  hemorrhage,  which 
was  proved  to  originate  from  one  ureter,  disappeared  permanently,  although 
the  exploratory  incision  of  the  kidney  in  question  showed  no  demonstrable 
pathologic  changes.  5.  Snch  cases  are  so  rare  that  they  may  be  considered 
purely  as  exceptions,  and  since  serious  disease  can  never  be  excluded  clinically 
as  a  cause  for  obscure  cases  of  hematuria,  in  all  doubtful  cases  an  exploratory 
lumbar  incision  should  be  made,  especially  since,  according  to  experience,  this 
may  have  a  curative  effect  upon  the  hematuria. 

In  the  fir^t  session  of  the  Fourth  French  Congress  for  Urology  (October, 
1899 )  a  symposium  upon  "essential  hematuria'"  took  place.  Malherbe  and 
Leguen  maintained  that,  besides  hemorrhages  occurring  in  tuberculosis,  car- 
cinoma, and  lithiasis,  a  so-called  essential  hematuria  had  also  been  described 
which  is  apparently  independent  of  disease  of  the  urinary  organs.  In  an 
accurate  analysis  of  the  cases  published  up  to  that  time,  particularly  those  c: 
which  had  been  pathologico-anatomically  investigated,  pathological  changes 
were  almost  invariably  noted  even  though  often  slight,  for  example,  calcareous 
incrustation  of  a  pyramid,  or  Blight  tuberculous  disease.  The  most  frequent 
cause  of  so-called  "  essential  hematuria  "  is  evidently  chronic  nephritis.  The 
quite  insignificant  sclerosis  of  the  renal  parenchyma,  as,  for  instance,  after 
contusion  of  the  kidney,  in  floating  kidney,  and  in  pregnancy,  may  remain  uni- 
lateral, and  not  necessarily  give  rise  to  further  symptoms  of  Bright' s  disease. 


HEMOPHILIA  449 

The  assumption  of  a  "  hemophilic  "  and  an  "'  angio-neurotic  "  hematuria  is  not 
justifiable.     "  On  peut  dire.  qu"il  n*y  a  pas  d'hematurie  essentielle:  toute- 
hematuries  .-out  symptomatiques  et  relevent  d'une  cause  generale  (toxique  ou 
infectieuse)  ou  d'une  affection  renale." 

Tedenat  also  questions  the  occurrence  of  true  essential  hematuria.  His 
own  experience  relates  to  four  cases  of  which  two  were  very  probably  con- 
nected with  nephrolithiasis :  nephrotomy  produced  a  cure.  In  another  case 
the  hemorrhage  ceased  after  the  removal  of  a  small  hydatid  cyst  of  the  kidney. 
In  the  fourth  case  the  cause  of  the  hematuria  was  a  carcinoma  of  the  colon 
compressing  the  ureter,  after  the  removal  of  which  the  hemorrhages  perma- 
nently ceased. 

Ponsson  also  denies  the  existence  of  essential  hematuria:  he  calls  atten- 
tion particularly  to  the  hemorrhages  which  result  from  the  retention  of  urine, 
in  consequence  of  floating  kidneys,  or  from  other  causes.  For  instance,  he 
observed  an  apparent  renal  hematuria  in  a  patient  in  whom  there  was  at  the 
left  renal  opening  of  the  ureter  a  mucous  membrane  valve  which  -  from 
time  to  time,  a  more  or  less  complete  retention  of  urine.  After  division  of 
the  valve  and  fixation  of  the  kidney  the  hemorrhage  -  -  L  In  another 
a  -tone  embedded  in  the  mouth  of  the  ureter  produced  the  hemorrhage. 

In  this  connection  Albarran  remarks  that  the  cases  of  so-called  essential 
hematuria  may  be  divided  as  follows:  1.  Hematuria  in  floating  kidney:  2.  In 
hydronephrosis :  3.  Hematuria  in  early  stages  of  chronic  nephritis.     Seven- 
teen cases  of  this  latter  form  are  already  mentioned  in  literature.     He  a 
another  case  occurring  in  a  patient  aged  fifty-three.     The1  hemorrhage  ce  - 
after  nephrotomy.     The  diagnosis  of  diffuse  parenchymatous  and  interstitial 
nephritis  was  confirmed  by  the  microscopical  examination  of  an  excised  por- 
tion of  the  kidney.     Boursier  emphasizes  that  so-called  essential  hematuria 
may  for  a  long  time  be  the  only  symptom  of  a  nephrolithiasis.     In  the  urate 
and  oxalate  diathesis  severe  hematuria   is  also  observed   without  any  -• 
being  presenl  :  it  may  be  that  the  small  crystals  produce  an  irritation  of  the 
renal  parenchyma  and  so  eventually  lead  to  periodic  hematuria. 

Hamonic  calls  attention  to  hematuria  as  a  premonitory  symptom  of 
tain  renal  affections  (parenchymatous  nephritis,  nephrolithiasis,  tubercul  -  -. 
carcinoma). 

Galland-Gleize  also  confirms  this  fact.     He  communicates  reports  of  four 

-  in  which  for  a  year  and  a  half  to  seven  year-  hemorrhage  had  pro 
the  disease  later  determined  (kidney-bladder  stone,  tumor  of  the  bladdei 

Loumean  agrees  with  those  who  do  not  believe  in  essential  hematuria  ex- 
when  the  microscopic   investigation  demonstrates  that  the  "renal  epi- 
thelium" is  normal.     Bui  we  should  require  even  more  than  this;  not  only 
the  integrity  of  the  epithelium  but  also  that  of  the  entire  parenchyma  should 
be  determined  after  a  portion  of  the  kidney  has  samined. 

This  will  be  still  insufficient  for  an  anatomical  diag     -  -.  as  the  pathol  _ 
process  i-  not  always  uniformly  distributed  over  the  entire  organ.     But.  apart 
from  the  actual,  diffuse  disease  of  the  kidney,  tin-  objection  i-  much  more  valid 
fur  those  diseases  of  tin-  renal  tissue  which  arise  from  a  focus,  such  as 
etc.     Here  the  investigation  of  one,  or  even  of  several,  portions  of  the  kidney 


450  THE  HEMORRHAGIC   DIATHESES 

might  show  perfectly  normal  conditions,  while  in  the  immediate  vicinity  of  the 
excised  portion  changes  might  have  taken  place  which  gave  rise  to  the  hemor- 
rhage ! 

Pasteau  has  described  a  typical  case  of  so-called  essential  hematuria  in 
floating  kidney.  Here  the  hemorrhages  were  connected  with  severe  attacks  of 
renal  colic,  and  were  permanently  relieved  by  nephropexy. 

In  opposition  to  many  other  authors,  Castan  believes  in  an  actual  essen- 
tial hematuria,  as  a  proof  of  which  he  mentions  the  following  typical  case: 
A  woman,  during  the  menopause,  and  for  a  period  of  several  months,  had 
very  profuse  hematuria  without  the  slightest  symptom  of  nephritis  being  evi- 
dent. Complete  and  permanent  cure  was  effected  by  means  of  baths,  massage, 
etc.  In  Castan's  opinion,  a  disturbance  of  menstruation  may  cause  the  reten- 
tion in  the  body  of  certain  toxins  which,  without  causing  demonstrable  disease 
of  the  renal  parenchyma,  may  give  rise  to  hematuria.  To  this  category  the 
hematuria  of  the  pregnant  also  belongs :  "  La  f  emme  est  en  etat  de  toxhemie 
permanente." 

Guyon  declares  that  among  the  causes  of  severe  threatening  renal  hemor- 
rhages congestive  conditions  occupy  the  front  rank.  The  kidneys,  however, 
macroscopically  and  microscopically,  may  present  no  changes  to  explain  the 
congestion.  He  admits,  of  course,  that  renal  hemorrhages  may  lie  due  to 
inflammation,  neoplasms,  stone,  etc.  Guyon  mentions  cases  of  profuse  con- 
gestive renal  hemorrhages  in  which  neither  at  the  operation  nor  at  the  autopsy 
could  pathological  changes  be  detected  in  the  kidney.  Especially  noteworthy 
are  three  observations  in  which,  during  pregnancy  and  lactation,  severe  conges- 
tive conditions  led  to  profuse  renal  hemorrhages. 

Briefly,  the  cases  are  as  follows : 

1.  A  woman,  aged  thirty-five,  previously  healthy,  in  the  eighth  month  of 
pregnancy  voided  for  fourteen  days  urine  of  a  coffee-brown  color.  In  the 
eighth  month  of  her  third  pregnancy  hematuria  recurred  and  lasted  for  three 
weeks.  During  this  pregnancy  there  were  no  signs  of  nephritis.  Three 
months  after  this  last  labor,  sudden,  severe,  continuous  hematuria  appeared, 
and  debilitated  the  patient  greatly.  There  was  a  discharge  of  coagula,  with 
severe  pain  in  the  right  renal  region.  Up  to  this  time  the  patient  had  been 
nursing  her  child.  Upon  advice  she  ceased  nursing  the  child,  and  the  hemor- 
rhages immediately  stopped.  Eight  kidney  somewhat  enlarged;  irregular 
shape.  Diagnosis  :  Neoplasm  of  the  right  kidney.  Upon  lumbar  incision  and 
section,  kidney  found  to  be  perfectly  normal.  Suture;  recovery.  Hemor- 
rhage has  not  recurred. 

2.  Hematuria  in  the  course  of  the  fourth  and  fifth  pregnancies;  otherwise 
perfectly  normal  conditions. 

3.  Severe  hematuria  at  the  end  of  pregnancy;  sudden  stoppage  after  ter- 
mination of  labor. 

The  same  author  mentions  two  other  cases  of  hematuria  during  preg- 
nancy. A  total  of  twelve  cases  of  this  kind  is  found  in  literature.  Guyon 
does  not  believe  that  these  pregnancy  hematurias  are  to  be  looked  upon  as  true 
essential  hematurias.  Besides  mechanical  causes,  inflammatory  changes  which 
lead  to  congestion  evidently  play  a  great  role. 


HEMOPHILIA  451 

Desnos  has  seen  in  a  large  number  of  gouty  patients  hematuria  which 
either  preceded  or  followed  the  attacks  of  gout.  This  gouty  hematuria  was 
either  accompanied  by  renal  colic  or  ran  its  course  without  pain;  the  condi- 
tion may  be  brought  about  by  "congestion,"  but  may  find  its  explanation  fre- 
quently in  the  influence  of  stone. 

On  account  of  limitation  of  space,  it  is  impossible  for  me  to  discuss  more 
minutely  the  literature  of  the  last  few  years,  and  I  shall  refer  only  to  the 
very  comprehensive  discussion  in  the  Berlin  Society  of  Internal  Medicine  in 
January,  1902,  of  the  excellent  article  of  Professor  Senator,  "  Renal  Colic, 
Renal  Hemorrhage  and  Nephritis/'  which  gives  succinctly  the  views  regard- 
ing these  questions  of  such  prominent  authors  as  Senator,  James  Israel,  G. 
Klemperer,  and  L.  Casper.  Any  one  desiring  to  learn  the  present  -talus  of 
this  question  will  find  in  this  source  material  upon  which  to  form  hi-  opinion, 
although  it  is  impossible  at  this  time  to  state  a  definite  conclusion.  The  sub- 
ject is  still  open  to  discussion,  and  the  combined  labors  of  the  surgeon  and 
the  internal  clinician  will  be  required  to  clear  it  from  all  doubt. 

I  must  emphasize  a  fact  which  is  frequently  observed,  that  in  hemophilia, 
hemorrhages  from  other  parts  of  the  body  cease  when  hematuria  occur-. 

Senator  was  the  first  to  throw  light  on  this  dark  Bubject,  and  it  is  cer- 
tainly owing  to  his  labors  that  some  renal  hemorrhages  have  been  recognized 
as  of  hemophilic  origin.  Although  some  have  doubted  whether,  in  hi-  case, 
the  condition  was  actually  renal  hemophilia  or,  on  the  contrary,  hemorrhage 
due  to  another  and,  at  that  time,  unrecognizable  cause,  there  is  much  in  favor 
of  his  view  that  cases  of  hereditary  renal  hemophilia  have  lately  been  observed 
(Attlee  and  Guthrie,  St.  Bartholomew  Hospital  Journal,  December,  1901,  and 
The  Lancet,  May  3,  1902,  xviii;  compare  also  Senator,  "  Renal  Diseases/'  2d 
edition,  p.  515,  additions).  No  matter  how  we  view  this  condition  it  is  greatly 
to  Senator*-  credit,  and  will  remain  so,  to  have  been  the  first  to  recognize  the 
just  importance  of,  and  to  throw  the  proper  scientific  light  upon,  the  under- 
Lying  cause ! 

Hematuria  must  not  be  looked  upon  as  the  only  local  hemorrhage  in  hemo- 
philia. I'nder  similar  circumstance-  pulmonary  and  gastric  hemorrhages  are 
occasionally  noted  in  bleeders,  at  the  age  of  puberty  or  even  later,  who  have 
until  then  been  \'v<<-  from  hemorrhage,  and  for  these  there  is  not  the  slightest 
anatomical  basis.  Cases  of  hematuria  have  awakened  interesl  especially  by 
their  being  unilateral,  and  also  because  it  has  been  possible  by  operative  pro- 
cedures to  make  an  exact  and  certain  diagnosis  during  life,  which  is  impossi- 
ble in  the  case  of  other  organ-,  particularly  of  the  stomach  and  lungs.  In  the 
future  the  diagnosis  of  essential  hematuria  will  necessitate  much  greater 
exactness. 

PROGNOSIS 

The  prognosis  of  hemophilia  is  unfavorable:  60  per  cent,  of  hi lera  suc- 
cumb before  the  eighth  year  of  life  and  only  11  per  cent,  reach  the  twenty- 
rod   pear.     After  puberty  the  chance-  are  somewhaf  better;  but,  even  in 

later  life,  a  -light    injury   may  terminate  fatally.      In  a    family   in    Finland   in 

five  generations  Crom  a  Btock  not  previously  hemophilic  fourteen  male  descend- 


452  THE  HEMORRHAGIC  DIATHESES 

ants  succumbed  directly  to  hemorrhage.     The  first  symptoms  of  the  disease 
were  noted  after  the  children  had  reached  the  age  of  six  months. 


TREATMENT 

General  prophylaxis.  On  account  of  the  hereditary  nature  of  the  disease, 
and  in  view  of  the  fact  that  the  affection  is  mainly  transmitted  by  the  female, 
it  is  obvious  that  the  proper  restriction  of  marriage  would  lessen  hemophilia. 
From  considerations  of  this  kind  laws  have  been  framed  in  accordance  with 
which  the  question  of  marriage  in  bleeder  families  should  be  considered.  The 
fundamental  rules,  based  upon  Grandidiers  rich  experiences  in  this  respect, 
are  as  follows : 

1.  All  females,  members  of  bleeder  families,  whether  they  themselves  are 
bleeders  or  not,  are  to  be  advised  not  to  marry. 

2.  All  male  members  who  themselves  are  not  bleeders  may  unquestionably 
be  permitted  to  marry. 

A  male  bleeder  is  only  to  be  dissuaded  from  marrying  if  it  can  be  proven 
that  in  his  family  hemophilic  males  have  reared  hemophilic  children,  although 
the  males  in  question  married  healthy  women  from  healthy  families. 

A  factor  which  is  said  to  favor  hemophilia  is  the  intermarriage  of  rela- 
tives. Whether  this  is  justifiable  or  not  is  difficult  to  determine.  So  far  as 
we  have  positive  knowledge,  the  conditions  are  the  same  as  in  the  intermarriage 
of  relatives  generally.  There  can  be  no  doubt  that  professional  prohibition 
of  marriage  has  very  little  effect.  The  desire  of  a  hemophilic  family  to  see 
a  daughter  married  may  be  much  stronger  than  the  fear  that  from  the  marriage 
bleeders  may  be  born. 

Of  paramount  importance  in  combating  hemophilia  is  individual  prophy- 
laxis. This  is  to  begin  as  soon  as  the  child  is  born,  and  during  the  years  of 
infancy  it  must  be  very  strict  in  accordance  with  the  experience  that  at  this 
age  the  hemorrhages  of  hemophiliacs  are  especially  prone  to  be  exceedingly 
serious.  In  nurslings  in  whom  there  is  a  suspicion  of  hemophilia,  all  attempts 
to  remove  slight  congenital  defects  are  absolutely  prohibited.  To  this  cate- 
gory belong  the  operations  for  hare-lip,  malformation  of  the  palate,  severing 
the  frenum  of  the  tongue,  the  operation  for  syndactylism,  the  removal  of  naevi, 
etc.  Eitual  circumcision  of  the  children  of  Jewish  and  Mohammedan  families 
is  to  be  strictly  prohibited.  In  girls  the  usual  piercing  of  the  lobe  of  the  ear 
for  earrings  must  be  omitted.  Experience  shows  that  vaccination  of  hemo- 
philiacs does  not  give  rise  to  threatening  hemorrhage;  it  may  therefore  be 
practised  in  infants  (and  also  re-vaccination)  without  danger.  Great  atten- 
tion must  be  paid  to  the  teeth  in  the  children  of  bleeder  families.  The  peri- 
odical observation  of  the  teeth  by  a  thorough  and  experienced  dentist,  and 
the  careful  treatment  of  even  the  slightest  affections  of  the  teeth  are  necessary 
in  order  to  preserve  them.  In  view  of  the  extreme  danger  of  surgical  operations 
upon  the  oral  cavity,  particularly  extraction  of  the  teeth,  care  must  be  exercised 
to  prevent  such  operations  in  so  far  as  possible  in  children  of  bleeder  families. 
The  application  of  leeches,  blisters,  wet-cups,  in  children  as  well  as  in  adult 
bleeders,  is  to  be  avoided.     When  the  children  begin  to  go  about  by  them- 


HEMOPHILIA  453 

selves,  their  play  with  other  children  is  to  be  watched.  The  nurse  must  be 
instructed  to  see  that  the  children  do  not  injure  themselves;  their  toys  are 
to  be  so  chosen  that  injury  to  the  skin  may  be  avoided.  Hemophilic  children 
must  not  be  chastised.  As  soon  as  the  children  are  intelligent  enough,  they 
and  their  playmates  are  to  be  instructed  that  injuries  by  falling  or  blows, 
a  prick  with  a  needle  or  pen,  should  be  avoided.  If  the  children  are  sent  to 
school  the  parents  should  inform  the  teacher  that  the  pupil  is  a  member  of  a 
bleeder  family.  It  is  advisable  that  the  physician  instruct  the  teacher,  in 
so  far  as  may  be  necessary  for  the  welfare  of  the  child  while  in  school,  as  to 
the  Bymptoms  of  hemophilia.  The  teacher  will  then  understand  how  to  con- 
duct himself  toward  a  hemophilic  pupil,  and  what  instructions  he  should  give 
the  other  pupils  as  to  their  behavior  to  the  bleeder.  Hemophilic  children 
should  not  take  part  in  gymnastic  exercises;  they  should  never  be  subjected 
to  corporeal  punishment. 

In  the  choice  of  an  occvpation  the  bleeders  are  limited  at  once  by  the  cir- 
cumstance that  in  comparison  with  others  they  are  weak.  They  must,  there- 
fore, choose  occupations  in  which  groat  bodily  strength  is  unnecessary.  Those 
without  moans  should  be  advised  to  become  clerks  or  designers.  Among  the 
lighter  trades  they  should  not  be  taught  those  trades  in  which  slight  injuries 
are  apt  to  occur,  such  as  watch-making,  engraving,  paper-hanging,  and  that 
of  goldsmith  and  barber.  Bleeders  whose  circumstances  permit  may  with 
advantage  pursue  the  learned  occupations.  Such  students  should  not  take  part 
in  games,  nor  should  they  be  accepted  in  the  army. 

General  Treatment.  Eemophiliacs  should  be  placed  on  a  special  diet,  and 
fluids  which  .-lightly  stimulate  the  vascular  system  (alcohol,  tea  and  coffee) 
arc  to  be  avoided.  The  use  of  milk.  Lemonade,  orangeade,  etc.,  is  to  be  ad- 
vised. Solid  food  is  to  be  of  the  bland  kind  ;  spiced  food-  Bhould  be  prohibited. 
Vegetables  (particularly  fresh  vegetables,  fruit,  salads)  arc  beneficial.  The 
genera]  nutrition  i-  to  be  stimulated  by  baths,  cold  ablutions,  occasionally  sea 
bath-,  and  by  residence  in  the  country. 

Special  Treatment.  Attempts  have  Keen  made  to  control  the  disease  by 
the  administration  of  drugs.  In  a  case  reported  by  Wlckham  Legg,  the  use 
of  iron  chlorid  is  said  to  have  broughl  aboul  improvement,  bul  in  a  case  of 
my  own  this  was  ineffectual.  The  following  drugs  have  also  been  tested: 
Mineral  acid-,  sugar,  lead  acetate,  magnesium  Bulphate  and  sodium  Bulphate. 
Of  the  mineral  acids,  chiefly  upon  Werlhofs  advice.  Bulphuric  acid   in   the 

form  of  the  elixir  acidi   Halleri  has  1 n  employed.     The  freshly  expressed 

juice  of  lemons  has  been  warmly  advised.  From  this  the  deeply-rooted,  popu- 
lar belief  in  the  lemon  treatment,  and.  in  milder  cases,  the  orange  treatment, 
ha-  developed,  in  which  in  a  gradually  increasing  number,  from  one  to  ten 
lemon-  daily,  that  i-.  their  juice,  arc  consumed.  This  "  treatment  *'  is  con- 
tinued foT  from  -i\  to  eighl  weeks.  Bul  its  benefits  areas  slighl  as  from  the 
Long-continued  use  of  I  laller's  acid. 

The  -aline-  are  perhaps  of  use  in  the  sense  that  they  relieve  the  congestive 
condition-  which  play  a  role  in  hemophilia.  Genera]  strengthening  and  tonic 
remedies  have  frequently  l n  resorted  to  during  the  periods  (v<'  from  hem- 
orrhage; and  during  thi-  time,  and  also  when  any  -iirii-  portend  an  approach- 


454  THE  HEMORRHAGIC   DIATHESES 

ing  hemorrhage,  ergot,  lead  acetate,  hydrastis  canadensis,  as  well  as  opium 
and  silver  nitrate,  have  been  employed  to  combat  the  hemorrhagic  diathesis. 
Upon  the  whole  little  is  to  be  expected  from  the  drug  treatment  of  liemo- 
ph  ilia  ! 

Kegarding  the  treatment  of  special  hemorrhages  in  the  hemophiliac,  at- 
tempts must  first  be  made  to  control  the  hemorrhage  by  mechanical  means. 
The  member  is  to  be  elevated.  Occasionally  this  alone  is  sufficient.  Secondly, 
the  employment  of  local  styptics  comes  into  question,  iron  chlorid  and  gelatin ; 
under  some  circumstances  the  cautery  may  also  be  employed.  Sometimes  we 
succeed  with  tampons;  sometimes  by  the  application  of  a  rubber  bandage  to 
the  bleeding  member  and  by  compression  of  the  nearest  large  artery.  Some- 
times the  tying  of  a  large  vessel  becomes  necessary.  Hemard,  to  control  the 
hemorrhage  after  extraction  of  a  tooth,  tied  the  common  carotid  artery. 

D.  McKenzie  (British  Medical  Journal,  April  27,  1901)  reports  the  occur- 
rence in  a  hemophiliac  of  an  apparently  uncontrollable  epistaxis  which  yielded 
at  once  to  a  tampon  of  cotton  soaked  in  suprarenal  extract. 

E.  Heymann  {Münchener  med.  Wochenschr.,  1899)  reports  the  case  of  a 
bleeder  aged  twenty-eight,  who,  after  removal  of  the  tonsil,  suffered  from  severe 
hemorrhage  which  could  not  be  controlled.  Heymann  injected  under  the  skin 
of  the  thorax  180  c.c.  of  a  2.5  per  cent,  neutralized  and  sterilized  solution  of 
gelatin  in  a  physiologic  salt  solution  warmed  to  40°  C.  After  fifteen  minutes 
the  hemorrhage  ceased,  and  did  not  recur  for  thirty  hours.  The  injection  was 
twice  repeated,  and  the  hemorrhages  invariably  became  slighter.  Heymann 
concludes  from  this  that  an  increasing  coagulability  of  the  blood  was  pro- 
duced. 

Nichols  (Medical  News,  1898)  reports  the  history  of  a  hemophiliac,  twenty- 
four  years  old,  who,  while  intoxicated,  fell  upon  broken  glass  and  received 
extensive  incised  wounds.  For  seven  days  the  hemorrhage  could  only  be  par- 
tially controlled,  and  the  patient  showed  symptoms  of  a  dangerous  anemia; 
Nichols  then  poured  the  contents  of  a  culture  tube  filled  with  10  per  cent, 
gelatin  into  the  wound.     The  hemorrhage  permanently  ceased. 

My  own  numerous  experiments  with  gelatin  for  the  purpose  of  controlling 
severe  hemorrhages  and  in  the  treatment  of  aneurism  lead  me  to  doubt  the 
correctness  of  these  observations,  although  I  do  not  wish  to  discountenance  the 
occasional  use  of  gelatin  for  styptic  purposes.  But,  in  doubtful  cases,  we  must 
not  expect  great  results  from  its  employment. 

Adrenalin  locally  has  of  late  been  successfully  used  in  controlling  bleed- 
ing, and  is  worthy  of  trial  in  hemophilia  under  similar  circumstances. 

Of  internal  remedies  ergot  and  its  derivatives  have  been  used.  Their 
effect,  however,  in  the  fully  developed  disease  is  very  questionable. 

During  pregnancy  in  hemophilic  women  hemorrhages  indicate  artificial 
abortion  or  early  induced  labor  (Kehrer).  Broock  (Transactions  of  the  Chi- 
rurgical  Society  of  London,  1900,  page  103)  reports  the  case  of  a  woman, 
a  member  of  a  bleeder  family,  who  had  borne  two  children  with  well-marked 
symptoms  of  hemophilia,  and,  as  she  had  suffered  greatly  from  hemorrhage 
in  each  labor,  he  endeavored  to  prevent  it  in  the  third.  He  instituted  a  treat- 
ment which  had  for  its  purpose,  on  the  one  hand,  a  general  strengthening  of 


HEMOPHILIA  455 

the  entire  system  (change  of  air  in  combination  with  the  administration  of 
iron,  quinin  and  arsenic )  and.  on  the  other  hand,  the  increase  of  the  coagula- 
bility of  the  blood  (calcium  chlorid).  The  course  of  the  labor  was  in  exact 
accordance  with  his  expectations.  The  loss  of  blood  was  very  slight,  the  child 
showed  no  signs  of  hemophilia,  and  was  stronger  than  the  children  previously 
borne. 

The  treatment  of  the  hemophilic  joint*  is  especially  important.  F.  König 
advises  the  following  method :  A  fresh  hemarthros,  above  all  in  a  bleeder,  is 
to  be  so  treated  that  the  patient  cannot  use  the  affected  joint :  moderate  com- 
pression decidedly  promotes  absorption.  The  question  whether  any  operative 
treatment  of  the  diseased  joint  is  permissible  König  answers  affirmatively,  in 
so  far  as  puncture  of  the  joint  is  concerned.  König  has  performed  puncture 
in  the  knee-joint  three  times,  twice  with  carbolic  acid  washing.  The  opera- 
tion was  always  harmless,  one  patient  was  much  improved,  and  the  other 
patient  was  cured :  bnt  König  advises  that  this  be  the  limit  of  operativ«'  pro- 
cedure. Of  three  patients  into  whose  joints  he  opened,  by  mistake,  supposing 
the  condition  to  be  tuberculosis,  two  bled  to  death,  and  one  after  many  hem- 
orrhages recovered,  bnt  bad  a  stiff  joint  remaining.  According  to  Guyot.  the 
treatment  of  the  hemophilic  arthropathies  in  the  acute  stage  must  be  entirely 
expectant;  later,  however,  puncture  of  the  joint  and  incision,  with  removal 
of  coagula,  is  said  to  facilitate  recovery,  after  which  recurrences  of  the  bleed- 
ing are  less  to  be  feared. 

The  latest  reports  regarding  the  therapy  of  bleeder's  joints  are  from  Hoffa's 
Clinic,  and  in  the  article  by  Gocht,  previously  referred  to.  great  importance 
is  attached  to  the  prophylaxis  of  hemophilia.  Improvement  of  the  general 
condition  by  good  food,  residence  in  pure  air.  and  hardening  of  the  body,  as 
well  as  the  avoidance  of  all  injuries  which  may  give  rise  to  hemorrhages,  are 
the  most  important  measures.  Boys  must  be  trained  to  this  from  the  onset, 
and  as  early  as  possible  they  must  be  taught  to  avoid  running,  jumping,  and 
other  active  children's  games.  If  it  is  known  that  the  child  is  a  bleeder  before 
it  learns  to  walk,  the  greatest  care  must  be  exercised.  The  joint  hemorrhages 
which  follow  the  most  insignificant,  scarcely  avoidable,  injuries  are  numerous 
enough,  aside  from  the  greater  injuries  which  may  bring  about  hemorrhage, 
and  must  be  carefully  guarded  against. 

The  first  lesion  to  be  described  in  Gochtfs  article  i-  a  fresh  effusion  of 
blood  into  the  knee-joint.  In  marked  cases  enormous  swelling  arises.  The 
joint  i-  so  tense  and  so  idled  with  fluid  that  the  resistance  of  the  capsule  of 
the  joint  checks  a  further  exudation  of  blood.  The  symptom-  are  the  same 
as  after  Bevere  contusions  of  the  joint,  except  thai  in  many  cases  from  the  i 
tin'  function  is  scarcely  disturbed.  Sometimes  the  knee  assumes  the  medium- 
flexure  position,  at  other  times  not  so,  or  only  for  a  few  hours  until  the  cap- 
sule bas  accommodated  it-elf  to  the  exudation.  The  treatment  varies.  Where 
there  is  decided  pain,  absolute  rest,  moist  compresses,  ice,  or  compression 
witb  bandages  may  be  beneficial;  in  other  cases  the  patients  are  kept  per- 
feetlv  quiel  or  are  permitted  to  walk  about  carefully.  Goch!  determined  from 
hi-  experience  in  the  Clinic  thai  generally  a  moderate  ose  of  the  joint  in  walk- 
ing has  no  injurious  effed  upon  the  absorption  of  the  effusion  in  the  joint. 


456  THE  HEMORRHAGIC   DIATHESES 

The  same  period  of  time,  about  two  to  four  weeks,  is  required  for  the  disap- 
pearance of  the  effusion,  whether  there  is  absolute  rest  or  use  of  the  joint. 
A  few  days  after  the  development  of  the  effusion  massage  is  to  be  cautiously 
begun,  not  upon  the  joint  itself,  but  in  parts  centrally  situated  from  the  joint. 
This  causes  no  pain  to  the  patient,  and  by  action  upon  the  peripheral  joint, 
absorption  is  stimulated.  At  the  same  time  this  treatment  prevents  the  mus- 
cular atrophy,  particularly  of  the  extensor  muscles,  which  so  readily  appears 
in  all  diseases  of  the  joints. 

In  the  majority  of  cases  these  measures  will  suffice  to  bring  about  absorp- 
tion of  the  effusion  of  blood,  especially  if  the  hemorrhages  have  not  as  yet 
been  frequent.  The  older  the  effusions  and  the  more  frequently  the  joint  has 
been  attacked,  the  less  rapidly  does  absorption  of  the  hemorrhage  take  place. 
Xevertheless,  here  also  the  treatment  must  be  expectant,  and  usually  recovery 
will  ensue. 

If  a  joint  has  entered  into  the  stage  in  which  it  resembles  hydrops  flbrinosus 
tubereulosus,  where  inflammatory  phenomena  dominate  the  clinical  picture, 
orthopedic  treatment  becomes  necessary.  In  opposition  to  König,  Gocht  main- 
tains that  only  when  the  patient  suffers  great  pain,  and  provided  the  physician 
is  absolutely  certain  in  the  diagnosis,  should  puncture  be  performed.  As  ex- 
perience has  taught  that  absorption,  even  although  slowly,  nevertheless  almost 
invariably  occurs,  removal  of  the  blood  need  not  be  resorted  to  except  for  im- 
perative reasons.  Here,  on  the  contrary,  orthopedic  treatment  should  be  em- 
ployed. Besides  the  measures  which  have  already  been  mentioned,  such  as  a 
position  of  rest,  compression,  and  (particularly  for  the  beginning  contracture) 
extension,  plaster  of  Paris  is  to  be  employed,  and,  above  all,  portable  apparatus 
so  as  not  to  keep  the  patient  too  long  in  bed.  A  brisement  force,  in  fact  all 
force  employed  for  extension  of  a  contracture  in  a  bleeder,  is  entirely  contra- 
indicated.  Rail-brace  apparatus,  well  manufactured  and  accurately  fitted  to 
the  extremity,  is  of  even  greater  use  in  the  third  stage  of  the  disease  in  which 
permanent  deformity  of  the  joints  has  sometimes  occurred.  The  many  ex- 
treme and  violent  stretchings  of  the  capsule,  and  the  inflammatory  processes 
following  these,  cause  an  increasing  damage  (i.  e.,  flaccidity)  of  the  capsule 
of  the  ligamentous  apparatus.  Just  as  in  tuberculosis,  not  only  flexion  but 
subluxation  and  abduction  of  the  tibia  posteriorly  and  outwardly  gradually 
occur. 

Changes  in  the  ends  of  the  bones  are  added  to  those  of  the  capsule  of  the 
joint,  so  that  we  have  a  mixed  form  of  destruction  and  distention-luxation. 
The  processes  of  contractures  which  occur  in  the  capsule,  ligaments,  muscles, 
fascia,  and  skin  increase  the  contracture  and  form  a  decided  hindrance  to  cor- 
rection. As  to  the  different  methods  of  extension,  surgical  monographs  must 
be  consulted.  Here  it  will  only  be  stated  that  the  patients  in  Hoffa's  Clinic, 
during  the  entire  time  of  extension,  are  out  of  bed  and  move  about.  When  the 
leg  is  completely  extended,  the  apparatus  is  worn,  according  to  the  severity 
of  the  case,  for  three  months  to  six  months  and  even  longer  to  prevent  relapses. 

The  employment  of  the  rail-brace  apparatus,  according  to  the  published 
reports,  has  given  excellent  results,  so  that  this  method  of  treatment  can  be 
warmly  recommended. 


MORBUS  MACÜLOSUS  WERLHOFII  457 

MORBUS   MACÜLOSUS   WERLHOFII    (PURPURA) 

(PURPURA  SIMPLEX,  HEMORRHAGICA,  RHEUMATICA  SEU   PELIOSIS 
RHEUMATICA  SCHOENLEINII) 

DEFINITION 

PUBPUEA,  on  account  of  its  obvious  manifestations,  has  boon  known  to 
physicians  for  a  very  long  time.  Superficial  hemorrhages  arising  from  every 
possible  cause  have  hitherto  been  grouped  together.  Hence  affections  in  which, 
according  to  the  presenl  state  of  our  knowledge,  the  purpura  forms  only  an 
auxiliary  or  symptomatic  phenomenon  (for  example,  diseases  with  jaundice  and 
hemorrhages)  have  been  regarded  as  independent  diseases.  From  the  mass  of 
diseases  in  which  purpura  occurs  upon  the  external  skin.  Werlhof,  in  the  year 
1775,  isolated  a  distind  clinical  picture  which  he  designated  purpura  hemor- 
rhagica, and  which  was  subsequently  named  after  him. 

Later,  other  divisions  were  made  in  the  group  of  hemorrhagic  dis< 
Purpurn  simplex  was  isolated  as  an  independent  affection,  and  a  variety  called 
purpura  urticans  was  also  described. 

Finally,  upon  the  authority  of  Schönlein,  the  term  peliosis  rheumatica 
came  into  use.  It  must  be  admitted  thai  such  a  division  was  justified  at  that 
period  :  it  was  accessary  at  a  time  when  the  conception  of  disease  entities  rested 
chiefly  on  a  subtle  differentiation  of  clinical  symptoms.  From  this  point  of 
view  great  importance  was  attached  to  a  single  symptom,  as  is  shown  by  the 
fact  that  the  term  "  peliosis  rheumatica  "  rests  solely  on  the  observation  that, 
in  some  cases  of  purpura,  an  affection  of  the  joints  is  occasionally  noted.  The 
fact  was  Losl  Bight  of  that  the  latter  often  occurred  in  combination  with  all 
hemorrhagic  diseases,  noi  only  in  those  whose  clinical  pictures  belong  strictly 
to  purpura,  but  also  in  the  course  of  scurvy  and  hemophilia.  Of  course  the 
old  divisions  of  the  different  forms  of  purpura  are  no  longer  justified.  As 
a  matter  of  fact,  in  the  lasl  twenty-live  years  a  change  in  the  conception  of  pur- 
pura has  taken  place,  and  there  is  now  a  tendency  to  regard  all  purpuric  dis- 
eases as  related,  and  the  individual  forms,  previously  supposed  to  be  inde- 
pendent, are  regarded  from  a  common  standpoint.  Upon  the  basis  of  my 
.»wn  experience,  which  extend-  over  many  years  and  includes  exceedingly 
numerous  observations,  1  believe  strictly  and  absolutely  l/ml  ihr  individual 
purpuric  diseases  "/•<  /'"/  essentially  different,  but  are  due  h,  ihr  same  cause, 
and  only  vary  in  degree;  that  is,  ihr  "varieties"  depend  upon  Ihr  intensity 
of  I  In'  affection. 

Occasionally  these  differences  are  clinically  presented  in  such  a  manner 
that  the  inexperienced  believes  he  has  before  him  entirely  different  clinical  pic- 
ture.- that  have  nothing  in  common  with  one  another.  Tin-  i-  a  difficult  held 
for  polemics,  and  convincing  arguments  are  useless  if  another  i>  fullv  ,.,,,,_ 
vinced  to  the  contrary.  The  only  method  leading  to  conviction  is  minutely, 
carefully,  and  without  prejudice  to  weigh  all  the  fact-  bearing  upon  the  ques- 
tion. 1 1  will  then  become  manifesl  that  all  these  variations  of  the  disease  form 
indefinable  transitional  stages  which  merge  into  each  other,  and  only  by 
greal  circumspection  can  differentiation-  !„•  made.     The  standard  of  identity 


458  THE  HEMORRHAGIC  DIATHESES 

accepted  by  me  has  been  exceeded  by  other  authors  (e.  g.,  Schwimmer  and 
Scheby-Buch)  who  are  not  satisfied  with  the  inclusion  of  the  various  forms  of 
purpura,  but  desire  also  to  include  scurvy  in  this  clinical  group ;  other  authors 
even  add  hemophilia. 

Apart  from  the  facts  demonstrated  by  bacteriology,  which  it  is  hoped  will 
be  more  certainly  confirmed  in  the  near  future,  purpura  is  an  affection  due 
to  the  action  of  unknown  deleterious  agents,  occurring  sporadically  and  show- 
ing a  transitory  tendencv  to  different  varieties  of  hemorrhage.  In  contrast 
to  hemophilia  there  is  no  congenital  or  hereditary  factor,  and,  unlike  scurvy, 
there  is  no  tendency  to  epidemiologic  and  endemiologic  distribution,  and  the 
hemorrhages  are  not  associated  with  severe  constitutional  manifestations. 
Scurvy  is  distinguished  by  the  fact  that  it  not  only  occurs  sporadically  but  also 
epidemically  or  endemically.  More  characteristic,  however,  is  its  dependence 
upon  external  conditions ;  it  is  almost  invariably  the  expression  of  severe 
nutritive  disturbance  produced  by  obscure  diseases  or  by  the  long  continuance 
of  insufficient  or  improper  food. 

Morbus  maculosus  Werlhofii  differs  essentially  from  hemophilia  in  the 
fact  that  it  unquestionably  belongs  to  the  acquired  diseases,  in  which  the 
factor  of  heredity  is  never  operative.  It  has  no  congenital  characteristics, 
such  as  are  so  peculiar  to  hemophilia. 

This  is  also  a  distinguishing  factor  between  scurvy  and  hemophilia.  Un- 
like the  scorbutic  patient,  the  bleeder  is  frequently  well  nourished  and  strong. 
Except  in  his  tendency  to  spontaneous  hemorrhage  he  may  be  looked  upon  as 
quite  normal.  In  the  comparison  of  hemophilia  with  related  diseases  in  the 
group  of  the  hemorrhagic  diatheses,  one  peculiarity  of  hemophilia  is  particu- 
larly prominent;  it  is  not  a  pathologic  process,  but  a  permanent  condition 
which  manifests  itself  sometimes  in  consequence  of  known,  at  other  times  of 
unknown,  causes. 

In  accordance  with  these  views,  we  shall  consider  the  purpuric  affections 
together,  but  we  shall  not  forget  the  older  clinical  divisions;  we  shall  bear  in 
mind  that  between  the  individual  forms  of  the  disease  transitional  stages 
occur,  and  that  the  barriers  between  them  are  artificial. 

The  conception  of  purpura  as  a  particular  chapter  of  special  pathology  pre- 
supposes the  exclusion  of  all  the  affections  which  are  combined  with  hemor- 
rhages of  the  skin,  which  hemorrhages,  however,  prove  nothing  essential  or 
definite,  but  are  only  a  single  symptom  in  the  entire  picture.  Among  such 
affections  are :  Hemorrhagic  variola,  typhoid,  acute  atrophy  of  the  liver,  phos- 
phorus poisoning,  sepsis,  ulcerative  endocarditis,  pernicious  anemia,  leukemia, 
yellow  fever,  icterus  gravis,  snake-bite  poisoning,  etc. 

Purpura  should  be  differentiated  only  when  the  hemorrhages  exist  alone 
or  dominate  the  entire  clinical  picture.  Of  course,  in  investigating  the  disease, 
a  sequel,  such  as  the  resulting  anemia,  is  of  minor  importance. 

ETIOLOGY 

In  most  cases  it  is  impossible  to  determine  any  immediate  cause  for  the 
disease;  the  affection  appears  in  typical  cases  spontaneously.  Cases  of  this 
kind  have  led  to  the  belief  that  scurvy,  which  may  arise  under  similar  condi- 


MORBUS  MACULOSUS  WERLHOFII  459 

tions,  is  identical  with  purpura,  so  that  the  latter  has  been  designated  as  the 
milder  and  more  acute  form  of  scurvy.  This  view,  as  we  have  shown,  is 
incorrect,  even  though  there  is  occasionally  a  mild  affection  of  the  gums  in 
Werlhofs  disease.  Often  the  symptoms  of  purpura  hemorrhagica  appear  dur- 
ing convalescence  from  severe  infectious  diseases,  particularly  after  enteric 
fever  and  malaria. 

In  rachitic  children,  as  well  as  during  pregnancy  and  in  labor,  the  affection 
has  also  been  noted.  Isolated  reports  have  been  given  of  toxic  forms  of  pur- 
pura. The  affection  has  also  been  observed  after  the  inhalation  of  poisonous 
gases. 

In  the  ecchymoses  which  are  distributed  so  numerously  over  the  entire 
body  it  is  often  possible  to  demonstrate,  in  the  substance  which  occludes  the 
capillary  vessel,  the  cause  of  the  entire  affection.  In  the  multiple  capillary 
hemorrhages  of  septic  affections,  which  show  to  the  naked  eye  white  centers 
in  tbe  midst  of  the  effused  blood,  occlusion  of  the  capillaries  and  capillary 
veins  with  emboli  of  micrococci  may  frequently  be  determined.  So  in  hemor- 
rhagic smallpox  bacteria  are  found  in  the  hemorrhagic  and  purulent  foci 
of  the  external  skin  and  in  the  internal  organs,  the  spleen,  kidneys  and  lung-. 
In  the  retinal  hemorrhages  of  metastatic  ophthalmia,  I  was  also  able  to  find 
masses  of  bacteria  in  the  occluded  vessel,  centrally  or  removed  from  the  foci, 
whereas  in  other  cases  which  were  evidently  of  septic  nature,  this  proof  could 
not  be  demonstrated.  This  attempt  to  find  thrombi  in  the  vessels  has  failed 
entirely  in  many  cases  of  hemorrhagic  exanthems.  In  many  other  diseases 
and  intoxications  the  most  important  clinical  symptoms  of  which  consist  of 
hemorrhagic  conditions  (cholera,  plague,  yellow  fever,  anthrax,  poisoning  from 
snake-bite  petechial  typhus,  etc.)  occlusion  of  the  capillaries  in  the  sur- 
roundings or  in  the  center  of  the  ecchymoses  have  not  been  manifest,  and  we 
have  been  forced  to  the  conclusion  that  zymotic  substances,  ferment  bo. 
ptomains  or  toxins  produce  the  hemorrhagic  diathesis. 

How  this  occurs,  whether  they  alter  the  blood  directly  and  thus  cause  occlu- 
sion of  the  capillaries,  or  whether  they  affect  the  walls  of  the  vessels  in  their 
structure,  or  in  their  functions  as  muscular  and  nervous  apparatus,  we  do  not 
know. 

Whether  in  morbus  maculosus,  that  is,  purpura  hemorrhagica,  microorgan- 
isms ot  their  toxins  circulate  in  the  blood,  exerting  a  deleterious  effecl  upon 
it  or  upon  the  membranes  of  the  vessel,  and  lead  to  the  multiple  ecchym 
which  are  typical  of  this  disease,  has  not  been   ascertained   with  certainty, 
although  such  a  \  iew  is  likely.      The  facts  at  hand  are  Qol  generally  accepted. 

Few  authors  have  found  well-characterized  microorganisms  as  the  cause 
of  purpura.  Ajello,  who  in  a  case  of  purpura  demonstrated  methemoglobin  in 
the  Bpectrum  of  the  blond,  assumes  that  purpura  hemorrhagica  may  arise  by 
autointoxication  from  the  intestinal  tract  as  the  result  of  absorbed  products 
of  proteid  decomposition;  Schwab  also  believes  an  action  of  toxins  to  be  the 
cause  of  thi-  disease.  In  other  forms  of  purpura  which  arise  in  connection 
with  infection-  diseases,  the  Mod«!  has  been  examined  for  bacteria,  only  in 
pari  with  a  positive  result.  Earlier  author-,  such  as  Batemann  and  Grisolle, 
have  looked  upon  certain  form-  of  purpura  as  infection-  and  contagious;  and, 


460  THE  HEMORRHAGIC  DIATHESES 

in  a  number  of  cases  of  purpura,  as  is  evident  from  later  investigations,  the 
proof  of  bacillary  disease  has  been  shown.  Bacilli  were  found  by  Klebs,  Ceci, 
Reher,  Demme,  Vessalle,  Gendre,  Ginnard,  Simon-Legrain,  Jones,  Tizzoni, 
Giovannini,  Kolb-Petrone,  Babes  and  Letzerich;  Hanot  and  Luzet,  Widal  and 
Therese  found  streptococci;  Lebreton  and  I  each  found  staphylococci  in  one 
case;  negative  findings  on  the  other  hand  have  been  mentioned  by  Marfan, 
Legendre,  Demys  and  others. 

The  opinion,  especially  maintained  by  Pctrone,  that  purpura  hemorrhagica 
in  an  infectious  disease,  Letzerich  believes  he  has  proven  to  be  correct  by  bac- 
teriologic  investigation.  In  the  case  of  a  woman,  aged  twenty-five,  who  suf- 
fered from  a  prolonged  attack  of  this  disease,  who  was,  however,  cured,  he 
found,  in  1884,  small,  glistening,  round  granules  in  the  blood.  By  culture 
these  proved  to  be  the  spores  of  a  bacillus  which  he  described  and  depicted 
minutely  as  bacillus  purpura?.  With  several  generations  of  this  culture  a  large 
number  of  rabbits  were  infected  by  injection  into  the  abdominal  cavity,  and 
always  with  a  positive  result;  the  animals  showed  a  short  time  afterward, 
especially  in  the  ears,  circumscribed  dilatation  of  the  capillaries  with  succeed- 
ing hemorrhage,  injection  of  the  gums,  etc. ;  if  the  animals  were  killed,  sim- 
ilar hemorrhages  and  vascular  dilatations  were  found  in  various  portions  of 
the  body.  The  microscopic  investigation  showed  in  the  blood-vessels  in  many 
areas  the  previously  described  bacilli,  that  is,  their  spores.  These  were  found 
most  constantly,  and  were  most  numerous  in  the  enlarged  liver. 

Letzerich  in  this  connection  points  to  the  frequent  enlargement  of  the 
liver  in  the  human  affection.  This  is  not  to  be  construed  as  a  frequent  occur- 
rence, however;  in  the  organs  of  the  experimental  animals  he  found  very 
marked  accumulations  of  erythrocytes,  and  stasis  in  the  capillaries  due  to  this. 
Further,  in  the  areas  of  the  dichotomous  branching  of  the  smallest  vessels  hya- 
line plugs  developed  by  the  action  of  the  chemical  poison  produced  by  the 
bacteria  upon  the  albumin  of  the  blood.  To  these  vascular  plugs  he  refers 
on  the  one  hand  the  hemorrhages  into  the  organs,  and  on  the  other  hand  the 
decided  circulatory  disturbance.  The  bacillus  enters  the  human  body,  prob- 
ably through  the  mucous  membrane  of  the  oral  and  pharyngeal  cavities. 

Letzerich  believes  these  investigations  demonstrate  with  certainty  that  pur- 
pura hemorrhagica  is  a  chronic  infectious  disease,  and  points  to  its  analogy 
with  syphilis  and  malaria.  It  is  noteworthy  that  three  years  after  these  pri- 
mary researches,  and,  as  he  states,  in  consequence  of  them,  Letzerich  himself 
was  attacked  by  a  very  prolonged  purpura,  running  its  course  with  marked 
enlargement  of  the  liver,  and  from  his  blood  the  previously  described  bacillus 
was  cultivated. 

The  bacillus  described  by  Letzerich  has  some  similarity  to  the  bacillus 
anthracis,  particularly  in  regard  to  the  conditions  of  its  growth.  In  Koch's 
stab  cultures  both  formed  more  or  less  irregular  colonies  (flocculi),  the  middle 
point  consisting  of  net-like  threads  which,  toward  the  border,  ran  off  in  sheath- 
like bundles.  They  differ  decidedly,  however,  by  their  size  and  the  form  of 
the  spores.  Although  in  both  bacilli  a  segmentation  of  the  apparent  threads 
occurs  in  various  lengths,  those  of  purpura  are  much  smaller  in  their  length 
and  breadth.     Added  to  this  the  spores  of  Letzerich's  bacillus,  in  comparison 


MORBUS  MACULOSUS   WERLHOFII  461 

with  the  large  oval  structures  of  the  bacillus  anthracis,  are  very  small  and 
perfectly  round.  The  bacillus  purpura  liquefies  gelatin  with  great  difficulty — 
scarcely  at  all — and  only  at  high  temperatures  (25°  to  30°  C.)  in  the  surround- 
ing of  the  flocculi  (colonic-). 

In  the  petechias  of  man  and  of  the  experimental  animals  a  sheath-like 
arrangement  of  the  bacilli,  sometimes  with  segmentation,  is  noted  in  foci ; 
these  frequently  are  found  equidistant  from  each  other,  not  lying  closely 
together,  and  are  spores  beginning  to  develop. 

The  surface  of  the  stab  in  Koch's  nutritive  gelatin  shows  flat  crescentic 
groove-  which  are  only  recognizable  upon  close  observation. 

The  chemical  differences  must  also  be  mentioned.  The  bacillus  purpura? 
does  not  form  so  toxic  a  substance  (toxin)  as  the  bacillus  anthracis,  but  only 
a  feebly  acting  ptomain  corresponding  with  the  slight  evening  rises  in  tem- 
perature that  now  and  then  occur.  Pure  purpura  differs  in  this  respect  from 
the  acute  forms  of  purpura  (petechia1)  usually  observed  in  the  course  of  the 
infectious  diseases,  as  these  owe  their  origin  to  other  microorganisms. 

Even  with  cultures  of  the  third  relapse.  Letzerich  produced  purpura  in 
rabbits.  In  section-;,  through  small  petechia}  in  the  transverse  section  of  the 
capillary  net,  and  also  where  dichotomous  branches  pass  into  the  lumen  of  the 
same,  dense  proliferations  of  purpura  bacilli  were  readily  recognized  by  sim- 
ple methylene-violel  -taining. 

The  bacillus  purpura?  is  not  found  in  all  the  forms  of  its  development  in 
all  of  the  petechia?.  Toward  the  end  of  the  disease,  or  during  the  relapse, 
only  clumps  of  free  spores  and  individual  bacilli  are  observed.  Examination 
of  numerous  petechia'  is  then  necessary  to  find  the  cycle  of  development  of  the 
microorganism  as  described.  In  the  relapses  of  the  disease,  particularly,  we 
frequently  note  emboli  of  spores  which,  upon  superficial  observation,  may  be 
looked  upon  as  micrococci  emboli,  but,  upon  closer  study,  merely  from  the  cir- 
cumstance that  they  are  embedded  in  gelatinous  plugs,  their  development  from 
threads  and  rods  can  be  determined. 

Lockwood  also  belieyes  purpura  to  be  of  an  infectious  nature,  and  the 
bacillus  described  by  Letzerich  to  be  the  carrier  of  the  infection  and  pathogenic 
agent.  According  to  this  author,  the  very  acute  development  and  the  course, 
which  is  similar  to  that  of  an  infectious  disease,  favor  the  view  of  an  infec- 
tious development,  and  he  quoted  11  cases  from  literature.  Of  these  13  died 
in  from  forty-seven  hours  to  twenty-one  days.  He  is  also  inclined  to  look 
upon  purpura  simplex  and  purpura  rheiimatica  as  due  to  the  same  infection, 
but  showing  a  differenl  intensity.  Cases  of  purpura  which  ran  a  fatal  course 
in  -even  hours  have  never  to  my  knowledge  been  published  by  other-,  and 
under  no  circumstances  can  these  be  included  among  the  cases  of  pure  pur- 
pura :  the  mo-t  severe  case  of  fulminant  purpura  that  I  ever  -aw  ( to  be  detailed 
Later)  terminated  fatally  in  two  days. 

II.  Neumann  cites  cases  of  hemorrhagic  diathesis  of  the  newborn.  In  the 
firs!  case,  besides  the  staphylococcus  pyogenes  aureus  as  in  former  cases,  the 
bacillus  pyocyaneua  ß  waa  found.  He  doea  not  admit  a  direct  relation  of  the 
latter  to  the  hemorrhagic  diathesis,  but  attributed  the  diathesis  to  Byphilis 
which  was  present. 


462  THE  HEMORRHAGIC   DIATHESES 

In  another  case  (with  melena)  the  bacillus  lactis  aerogenes  was  found, 
but  to  this  he  ascribes  no  pathologic  importance. 

Lebreton  describes  in  a  young  girl  a  case  of  fatal  purpura  which  developed 
very  acutely  after  great  fright.  Large  confluent  ecchymoses  appeared,  from 
the  blood  of  which,  upon  culture,  the  staphylococcus  albus  and  the  staphylo- 
coccus aureus  were  obtained  in  mixture.  The  disease  was  therefore  looked 
upon  as  infectious  purpura. 

Wikner  also  found  the  staphylococcus  pyogenes  albus  in  a  case  of  morbus 
maculosus  Werlhofii. 

In  a  number  of  cases  of  purpura  I  have  examined  small  areas  of  the  skin 
covered  with  petechia?  which  were  excised  during  life,  and  I  have  never  been 
able  to  determine  the  presence  of  microbes. 

Later  investigations  and  reports  of  this  malady  are  not  at  hand ;  in  the 
last  four  volumes  of  the  Virchow-Hirsch  Year-Books,  I  have  not  observed  a 
single  report  of  purpura  in  man.  In  this  article  publications  up  to  the  year 
1898  have  been  referred  to. 

We  now  come  to  another  series  of  reports  which  had  their  origin  partly  in 
anatomical  studies  of  the  vessels  in  the  course  of  the  hemorrhage,  and  partly 
in  certain  experiments. 

Silbermann,  who  conducted  one  series  of  experiments,  started  from  the 
well-known  researches  of  Armin  Koehler,  who,  in  his  work  at  Dorpat  upon 
thrombosis  and  its  relations  to  the  fibrin  ferment,  mentions  a  series  of  experi- 
ments in  dogs,  in  which,  by  infusion  of  blood  very  rich  in  ferment,  a  disease 
resembling  Henoch's  purpura  (see  below)  was  produced,  inasmuch  as,  in  a 
short  time  after  the  transfusion,  multiple  capillary  ecchymoses  were  noted  in 
the  subcutaneous  cellular  tissue,  and  hematemesis,  hemorrhagic  diarrhea,  and 
intestinal  colic  occurred.  The  fulminant,  and  almost  invariably  fatal,  course  of 
the  pathologic  process  produced  by  Koehler,  on  account  of  the  great  amount  of 
ferment  contained  in  the  injected  blood,  caused  Silbermann  to  choose  a  method 
in  which  the  animals  either  did  not  die  or  did  not  succumb  so  rapidly,  and  in 
which  the  purpuric  spots  appeared  more  numerously  and  were  distributed  over 
the  entire  skin.  He  tried  this  plan :  The  dogs,  prior  to  the  ferment  intoxica- 
tion, received  small  doses  of  pyrogallic  acid  (0.05  per  kilogram  of  weight  of 
the  dog),  by  which  only  a  moderate  stasis  in  the  veins  and  capillaries  occurred. 

This  property  of  pyrogallic  acid  in  small  amounts  depends  upon  a  very 
slight  damage  to  the  blood,  a  slight  "shadow  formation"  and  fragmentation 
of  the  erythrocytes,  by  reason  of  which  the  circulatory  disturbance  occurs. 

In  a  number  of  dogs,  after  stasis  of  the  veins  and  capillaries  of  the  entire 
circulation  had  been  produced  by  suitable  doses  of  pyrogallic  acid,  Koehler's 
experiments  were  repeated,  with  the  expectation  that  the  cutaneous  capillaries, 
which,  like  all  other  capillaries  of  the  body,  were  under  high  pressure  with 
decided  strain  on  their  walls,  would  become  more  permeable  by  the  ferment 
blood.  As  a  result  of  these  experiments  it  was  shown  that  in  the  animals  thus 
prepared — by  injections  of  ferment  blood — thromboses  and  hyaline  vascular 
changes  could  be  invariably  produced  in  the  internal  organs,  less  constantly 
in  the  skin.  The  consequences  of  these  vascular  changes  were  multiple  hemor- 
rhages into  the  internal  organs  and  partially  also  into  the  skin. 


MORBUS  MACULOSUS  WERLHOFII  463 

Since  a  rupture  of  the  vessels  could  not  be  found  microscopically  (the 
proof  of  this  can  only  be  certainly  demonstrated  with  great  difficulty)  these 
hemorrhages  were  assumed  by  Silbermann  to  be  due  to  diapedesis,  and  this  to 
distention  of  the  vessel  walls.  The  vascular  changes  as  well  as  the  extravasa- 
tions are  themselves  consequences,  not  causes,  of  the  circulatory  disturbance, 
for  alteration  of  the  vessel  wall  never  occurs  alone  but  is  always  observed  in 
combination  with  thrombosis,  while  the  opposite  is  very  often  the  case.  The 
frequent  closure  of  the  capillary  area  by  thrombosis  may  be  explained  by  the 
lessened  rapidity  of  circulation  therein,  a  factor  which  greatly  favors  the 
occurrence  of  coagulation.  The  stasis  which  occurs  in  mild  cases,  and  is  fol- 
lowed by  thrombosis  in  the  more  severe  ones,  damages  the  vascular  wall,  how- 
ever, so  that  it  makes  it  permeable  to  the  passage  of  blood.  Indeed  this  stasis 
may  give  rise  to  fatty  degeneration  and  even  necrosis  of  the  vascular  cells. 

Since  "purpura"  with  swelling  of  the  joints,  hematemesis,  hemorrhagic 
diarrhea  and  intestinal  colic  had  been  experimentally  produced  in  animals  by 
means  of  a  dyscrasic  blood  the  question  arose  whether  human  purpura — no 
matter  in  what  form — might  also  be  explained  as  a  primary  disease  of  the 
blood.  Silbermann  believes  that  this  question  must  be  answered  in  the  affirma- 
tive, for  the  reason  that,  apart  from  certain  important  blood  findings,  the 
essentia]  connection  of  the  pathologic  phenomena  can  only  be  uniformly  ex- 
plained upon  the  basis  of  a  primary  disease  of  the  blood. 

The  hemorrhages  into  the  skin  and  into  the  gastro-intestinal  tract,  the 
hemorrhagic  vomiting,  the  colic,  and  the  swelling  of  the  joints,  which  occur 
in  severe  cases  of  purpura,  Silbermann  explains  as  due  to  a  primary  blood 
alteration  which  leads  to  a  slowing  of  circulation,  stasis  and  formation  of 
thrombi.  Upon  the  basis  of  these  circulatory  disturbances  congestive  hemor- 
rhagic occur,  and  also  hemorrhages  which  follow  as  the  result  of  the  occlusion 
of  vessels,  and  give  rise  to  necrosis  of  the  tissues.  These  stases  and  thrombi 
damage  not  only  the  gastro-intestinal  canal,  but  also  the  tissue  of  the  liver, 
the  kidney-  and  the  myocardium,  and  may  cause  fatty  degeneration  of  the 
cell-  ami  necrobiosis.  All  of  these  processes  were  observed  lately  by  Tizzoni 
and  (iiovannini  in  the  organs  of  a  girl  succumbing  to  severe  purpura.  There 
was  occlusion  of  the  vessels  which  had  produced  hemorrhage  and  necrosis  of 
tissue,  ami  al-o  caused  the  vascular  changes  previously  observed  in  man  and 
animal  attacked  by  purpura.  Silbermann  regards  it  as  certain  that  this  de- 
generation of  tin-  walls  of  the  vessels  IS  secondary,  because,  jn  hi-  experiments, 

all  stages  of  the  obliteration  of  vessels  have  been  followed,  ami  the  hyaline 
deposits  have  been  Bhown  to  be  result-  of  this  obliteration. 

In  literature  similar  \ iews  in  regard  to  the  nature  of  purpura  are  constantly 
met  with.  Thus  Green,  du  Castel,  Dusch,  Mackenzie,  Krau--  and  others 
believe  that  there  are  alterations  of  the  blood  in  certain  forms  of  purpura. 
Leloir,  who  ha-  al-o  observed  stasis  in  the  vessels,  differentiates  a  purpura 
"//<//•  modification  des  vaisseaux"  ami  a  purpura  "  /»n-  modification  </'/  sum/." 
Rieh]  and   v.    Kogerer,  on   the  other  hand,  believe  the  alteration   in  the  vet 

to  be  the  primary  condition  :  the  change  in  the  blood,  i.  e..  the  thromboses,  the 
secondary.  The  latter  says,  in  his  article  regarding  the  development  of  cuta- 
neous hemorrhages:  "On  the  whole  there  can  he  n<(  doubl  that  the  thrombi 


464  THE  HEMORRHAGIC  DIATHESES 

which  have  been  found  are  the  direct  cause  of  the  hemorrhage.  The  thrombi 
themselves  are  due  to  the  combined  action  of  local  and  general  causes ;  hence 
vascular  changes,  as  is  evident  from  the  constancy  of  the  finding,  play  the 
main  role  even  if  they  do  not  form  a  conditio  sine  qua  non"  The  view  of  v. 
Kogerer  that  the  thrombi  are  due  to  general  and  local  causes  is  also  the  opin- 
ion of  Silbermann  who,  however,  looks  upon  the  alteration  of  the  blood  as  the 
general  cause,  and  the  pathologic  change  in  the  blood  current  of  the  capil- 
laries (due  to  ferment  blood)  as  the  local  cause.  On  account  of  these  con- 
stant anatomic  findings  v.  Kogerer  calls  purpura  a  primary  disease  of  the 
vessels,  while  Silbermann  believes  these  changes  to  be  secondary.  Other  ob- 
servers, for  example,  Leloir,  have  not  noted  the  constant  occurrence  of  dis- 
ease of  the  vessels.  He  believes  the  occlusion  of  the  vessels  to  be  embolic, 
while  v.  Kogerer  and  Silbermann  declare  this  to  be  thrombotic. 

v.  Kogerer  defines  the  result  of  his  investigations  in  purpura  in  the  follow- 
ing scheme : 

(a)  Vascular  disease, 

( b )  Thromboses, 

(c)  Extravasations  of  blood, 

(d)  Pigmentation. 

While  Silbermann  comes  to  the  following  conclusions : 

(a)  Thromboses, 

(b)  Vascular  disease, 

(c)  Extravasations  of  blood, 

(d)  Pigmentation. 

As  will  be  noted  these  authors  agree  that  the  disease  of  the  vessels  is  the 
underlying  cause  of  the  hemorrhages,  but  Silbermann  looks  upon  stasis  and 
thrombus-formation  (in  the  small  veins  and  capillaries)  as  the  primary  condi- 
tion which  leads  to  disease  of  the  vessels ;  while  v.  Kogerer  believes  thrombus- 
formation  to  arise  as  the  result  of  the  disease  of  the  vessels.  The  latter  con- 
dition in  either  case  causes  hemorrhage. 

v.  Kogerer  examined  13  cases  which  ran  their  course  with  cutaneous  hemor- 
rhages; in  these  he  excised  particles  of  the  skin,  and  studied  microscopically 
the  changes  in  the  different  layers  of  the  cutis  and  subcutaneous  cellular  tissue. 
The  diseases  represented  were  scurvy,  morbus  maculosus,  tuberculosis  pul- 
monum, carcinoma  ventriculi,  marasmus  senilis,  peliosis  rheumatica,  sepsis, 
vitium  cordis,  etc.  In  all  cases  in  which  careful  search  was  made  thrombi 
were  found.  These  were  mostly  situated  in  the  small  venous  trunks,  but  were 
also  found  in  the  small  arteries.  Besides  this  many  minute  arteries  and 
capillaries  were  filled  with  fibrin  coagula  and  blood-corpuscles,  and  it  was 
impossible  in  some  cases  to  decide  whether  the  condition  was  one  of  actual 
thrombosis  or  only  a  vessel  surcharged  with  blood  (  !).  The  thromboses  were 
occasionally  numerous,  at  other  times  more  scant,  and  frequently  repeated 
search  was  necessary  to  find  them.  In  some  cases  the  degeneration  of  the  vas- 
cular wall  was  conspicuous. 

Eiehl,  even  prior  to  v.  Kogerer,  invariably  found  changes  in  the  blood- 


MORBUS  MACULOSUS  WERLHOFII  465 

vessels  of  the  cutis  and  of  the  subcutaneous  connective  tissue  in  scurvy,  morbus 
maculosus,  and  purpura  rheumatiea,  as  well  as  in  the  purpura  of  cachectic 
individual-. 

In  cases  of  scurvy  and  morbus  maculosa-,  diffuse  endarteritis  and  thick- 
ening of  all  the  coats  of  the  vessels,  hyaline  degeneration,  and  partial  fatty 
degeneration  of  the  same,  narrowing  of  the  lumen  and  proliferation  of  the 
endothelium,  could  (he  said)  be  invariably  demonstrated.  Besides,  it  was 
found  that  in  some  areas  the  connective  tissue  surrounding  the  vessels  and  the 
fatty  tissue  showed  decided  round-cell  infiltration. 

In  the  hemorrhagic  areas  fresh  and  more  or  less  altered  extravasations 
of  blood  were  observed,  i.  e.,  coarsely  granular  or  flaky  blood  pigment,  em- 
bedded between  the  bundles  of  connective  tissue  and  in  the  cell  infiltration-. 
On  the  other  hand.  Riehl  could  never  detect  pigmented  leukocytes,  as  in  the 
case  of  Addison's  disease,  etc.  In  both  processus  the  cross-striated  muscles 
which  were  examined  showed  fatty  degeneration. 

in  purpura  rheumatiea  and  purpura  cachecticorum  as  well  as  in  a  case 
of  hemorrhage  into  the  shin  occurring  after  sepsis,  similar  changes  could  be 
determined,  but  the  vascular  alterations  and  infiltrations  of  the  perivascular 
connective  tissue  were  Less  marked.  In  all  instances  the  reticular  stratum  of 
the  cutis  showed  the  greatesl  implication  of  the  large  arteries;  next  to  these 
the  vessels  of  the  adipose  tissue,  and  least  marked  the  vascular  layers  of  the 
subpapillary  tissues. 

In  all  cases  examined  by  v.  Kogerer  the  vascular  changes  which  have  been 
described  could  be  demonstrated,  and  he  therefore  concludes  their  certain 
connection  with  the  hemorrhages.  Ee  assumes  further  that  the  hemorrhage 
results  per  rhexin.  But  in  order  that  the  pathologically  changed  layers  of 
the  vessels  shall  rupture  during  life,  other  local  conditions,  he  believes,  must 
be  simultaneously  active.  These,  in  his  opinion,  consisl  in  thromboses  of  the 
smallest  arteries,  and  he  refer-  to  the  hemorrhages  in  the  center-  of  which, 
in  septic  endocarditis  and  similar  processes,  emboli  of  micrococci  are  found 
(  Weigert,  Litten  and  other- 1. 

Besides  the  early  investigations  of  Eayem  and  Stroganow,  which  have  been 
referred  to,  the  more  recent  one-  of  Leloir  and  Rieh)  must  be  mentioned. 
They  confirm  the  finding  of  vascular  changes  in  the  reticular  Btratum  of  the 
cutis  and  in  other  areas  of  the  body,  the  changes  consisting  of  thickening, 
hyaline  degeneration,  fatty  degeneration  of  the  endothelium,  and  formation 
of  thrombi,  v.  Recklinghausen  also  find-  these  causes  of  hemorrhage;  I  shall 
quote  two  of  hie  remark-  relating  to  this  condition  (Handbook  of  General 
Pathology  of  the  Circulation  and  of  Nutrition)  :  "  A-  regards  many  cases  of 
multiple  capillary  hemorrhage,  formerly  included  in  the  category  of  the  hem- 
orrhagic diathesis  or  of  blood  dissolution,  etc.,  we  are  able  to-day  to  prove 
that  they  occur-  mechanically,  by  occlusion  of  the  smallest  vessels  with  indif- 
ferent material,  or  with  one  of  specially  Beptic  constitution,"  and  further: 
"Occasionally,  as  the  resuH  of  obstruction  of  a  vein,  capillary  hemorrhi 
also  appear  in  the  area  of  stasis;  this  is,  however,  quite  rare,  and  we  may 
therefore  conclude  thai  here  complications,  for  example,  senile  vascular 
changes,  are  operativ» ." 
81 


466  THE  HEMORRHAGIC  DIATHESES 

Despite  the  report  that  by  anatomical  investigations  vascular  changes  have 
been  found  in  the  ecchymoses  of  neighboring  capillaries  as  well  as  in  the 
smallest  arterial  and  venous  vessels,  in  my  opinion  no  clinician  will  admit 
these  to  be  a  constant  etiologic  factor  in  purpura.  In  order  to  reject  absolutely 
the  theory  that  the  described  vascular  changes  are  the  cause  of  such  processes, 
one  must  have  witnessed  how  the  normal  skin  of  the  entire  body  may  be 
covered  by  hemorrhages  in  the  course  of  a  few  hours,  so  that  the  entire  surface 
appears  spotted  like  the  skin  of  a  tiger  or  a  leopard.  I  refer  here  to  the 
illustration  I  gave  in  Notlmagel's  "  Special  Pathology  and  Therapy,"  Part  III, 
vol.  viii.  Such  a  possibility  must  be  constantly  borne  in  mind.  We  shall 
discard  absolutely  the  assumption  of  a  vascular  disease  distributed  over  the 
entire  cutaneous  surface,  if  we  consider  the  appearance  and  disappearance  of 
the  affection  in  the  briefest  time,  the  recurrence  and  repeated  recurrence  after 
varying  intervals,  and  the  final  complete  recovery  from  the  disease.  That  the 
vessels  in  the  hyperemia  areas  present  the  phenomenon  of  stasis  is  self-evident ; 
the  exit  of  blood  per  diapedesin  is  itself  the  final  and  most  extreme  phenomenon 
and  expression  of  each  extensive  stasis.  But  a  purpura  hemorrhagica  widely 
distributed  over  the  entire  body,  appearing  acutely,  and  sometimes  involving 
the  mucous  membranes  and  the  serous  membranes,  can  never  be  due  to  a 
hyaline  vascular  degeneration.  How  could  this  arise  so  suddenly  and  disappear 
so  rapidly?  I  admit  the  vascular  degeneration  as  a  cause  in  certain  cases 
running  a  severe  and  fatal  course,  particularly  the  forms  which  run  a  chronic 
course,  in  which  the  cutaneous  hemorrhages  represent  one  of  the  secondary 
symptoms  of  the  disease,  as,  for  instance,  in  senile  marasmus,  peliosis  cachec- 
ticorum  or  in  pulmonary  tuberculosis.  But  the  mild  cases  (ordinary  purpura) 
which  run  a  more  or  less  rapid  course,  repeatedly  appearing  and  disappearing 
again,  certainly  do  not  depend  upon  stasis  and  hyaline  vascular  degeneration 
but  on  internal  causes  entirely  unknown  to  us  at  the  present  time. 

The  many  microscopic  investigations  which  I  have  made  in  cutaneous 
hemorrhages  in  all  forms  of  the  hemorrhagic  diathesis,  and  particularly  my 
numerous  investigations  of  the  blood-vessels  of  the  eye  (the  optic  nerve,  the 
choroid  and  the  retina)  in  pernicious  anemia,  leukemia,  scurvy,  diabetes  and 
sepsis,  I  must  admit  have  given  results  which  are  by  no  means  satisfactory. 
In  many  hemorrhages  of  the  retina  in  these  diseases,  in  spite  of  the  most 
minute  and  careful  examination  of  numerous  sections  so  thin  that  they  per- 
mitted the  use  of  an  immersion  lens,  I  have  not  succeeded  in  detecting  vascu- 
lar changes  in  the  arterioles  or  capillaries  supplying  them.  The  conducting 
vessel  was  quite  intact,  and  each  blood-corpuscle  contained  in  it,  as  well  as 
the  nuclei  of  the  walls,  and  the  patent  lumen,  could  be  distinctly  recognized 
almost  up  to  the  bleeding  point,  where  frequently  a  dichotomous  division 
occurred.  The  two  branches  given  off  could  be  seen  for  a  short  distance  and 
were  quite  intact  until  they  disappeared  in  the  hemorrhage.  The  eye  of  the 
investigator,  no  matter  how  practised,  is  unable  to  see  in  the  midst  of  the  hem- 
orrhage which  completely  covers  the  arteriole  or  capillary  what  has  become 
of  the  vessel,  and  especially  whether  the  hemorrhage  has  occurred  per  diape- 
desin or  per  rhexin.  Hence  I  must  absolutely  reject  this  theory,  and  can  only 
compliment  those  observers  who  were  able  to  demonstrate  a  vascular  change 


MORBUS  MACULOSUS   WERLHOFII  467 

in  "  every  "  case.  At  this  point,  I  wish  to  refer  to  my  later  investigations 
of  the  vascular  changes  in  the  retinitis  of  Brighfs  disease,  which  are  soon 
to  be  published. 

The  conditions  are  not  very  dissimilar  in  hemorrhage,  occurring  as  the 
result  of  general  septic  disease,  although  they  really  do  not  belong  to  the  same 
category.  There  is  no  doubt  that  in  cases  of  sepsis  and  malignant  endocarditis, 
in  the  midst  of  cutaneous  hemorrhages,  occasionally  a  white  center  is  seen 
which  is  analogous  to  the  same  processes  in  the  retina.  Although  I  have 
sometimes  succeeded  in  recognizing  these  white  centers  as  small  infarcted 
blood-vessels  filled  with  micrococci,  this  finding  is  not  constant,  and  cannot 
be  proved  to  be  a  process  which  occurs  during  life;  under  no  circumstances 
can  conclusions  be  drawn  from  this  to  explain  the  multiple  cutaneous  hemor- 
rhages in  the  various  forms  of  purpura. 

How  far  an  infection  may  be  assumed  to  cause  the  disease  in  these  latter 
cases  must  remain  an  open  question  until  it  is  proven  whether,  and  to  what 
extent,  the  bacillus  purpura3  or  some  other  pathogenic  microbe  is  a  constant 
finding  in  the  blood  of  patients  suffering  from  morbus  maculosus.  If  later 
investigations  should  substantiate  this,  the  view  would  also  be  permissible 
that  the  toxins  or  ptomains  circulating  in  the  blood  lead  to  an  extensive  stasis 
formation  in  the  capillarie-  and  -mall  veins,  or  that  tiny  directly  alter  the 
blood,  thus  causing  occlusion  of  the  capillaries,  or.  finally,  that  they  affect 
the  vascular  walls  in  their  structure  or  in  the  functions  of  their  muscular 
and  nervous  apparatus  so  that,  for  example,  a  stasis  as  the  resull  of  paralytic 
dilatation  of  the  smallesl  vessels  might  take  place. 

That  the  Beveresl  cases  of  this  disease,  designated  as  purpura  fulminans, 
terminating  fatally  in  the  briefest  time,  are  of  an  infection-  character,  and  are 
probably  due  to  the  entrance  of  pathogenic  microorganisms  which  have  a  very 
deleterious  effect,  I  believe  to  be  true  beyond  doubt,  although,  unfortunately. 
thi-  has  not  as  yet  been  proven. 

As  a  rule  the  disease  is  not  frequent;  female-,  according  to  reports,  appear 
to  be  somewhat  more  predisposed  than  male-.  An  age  limit  does  not  exist, 
but  at  middle  life  attack-  appear  to  he  mosl  numerous.  The  aged  and  nurs- 
lings are  very  rarely  affected.  Nevertheless,  the  report  that  prior  to  the  fifth 
year  of  life  Bcarcely  any  cases  occur  i-  incorrect.  I  have  certainly  -ecu  quite 
a  number  of  cases  which  occurred  between  infamy  ami  the  tilth  or  sixth  year. 
The-c  cases  were  either  pure  "  purpura  -implex  "  or  "  purpura  hemorrhagica."* 

oi-  -iich  forma  a-  are  complicated  with  disease  of  the  joints  (peliosis  rheu- 
matica),  or,  lastly,  forms  in  which  not  only  cutaneous  hemorrhage  but  \\ 
tinal  -vmpt s.  particularly  vomiting,  intestinal  coli,-,  and  watery  or  hemor- 
rhagic diarrhea,  are  prominent,  in  quite  a  large  number  of  cases  which 
occurred  in  rachitic  children  in  the  Becond,  third  and  fourth  years  of  life 
the  only  symptom  was  attack-  of  cutaneous  hemorrhage,  and  after  repeated 
relapses  these  children  made  a  complete  recovery.     Here  also  the  female  sex 

wa-   in   the  majority. 

Immediate  ean-e-  can  he  determined  only  in  the  ran  The  d 

Seems  to  appeal-  "  spontaneously  and   primarily,"  and  either  to  e.\hau-t    it-elf 


468  THE  HEMORRHAGIC  DIATHESES 

ill  one  attack  or  to  extend  through  several  relapses.     In  isolated  cases  the 
duration  of  the  attack  may  be  many  months  or  even  years. 

Chilling  or  wetting  of  the  body,  damp  dwellings  and  insufficient  food  are 
cited  as  causes,  but  without  sufficient  reason.  Since  unfavorable  circumstances 
of  life  and  unhygienic  surroundings  reduce  the  bodily  resistance  and  increase 
the  predisposition  to  all  diseases,  this  is  naturally  the  case  also  in  the  hemor- 
rhagic diathesis.  We  see  poorly  nourished  individuals  with  poor  constitutions 
forming  by  far  the  great  contingent  of  sufferers  from  this  disease,  but  we  also 
find  the  disease  in  millionaires  who  live  in  luxurious  palaces,  and  who  can 
command  all  the  advantages  of  life  and  the  best  of  care. 

The  affection  always  occurs  sporadically  and  as  an  isolated  disease,  never, 
as  in  the  case  of  scurvy  with  which  it  is  often  confused,  showing  an  endemic 
or  epidemic  distribution. 

In  isolated  cases  intoxication  with  marsh  gas  has  been  reported,  but  prob- 
ably this  is  erroneous.  On  the  other  hand,  it  appears  to  be  absolutely  proven 
that  in  convalescents  from  enteric  fever  and  malaria,  or  after  these  diseases 
have  run  a  prolonged  course,  purpura  sometimes  follows.  I  have  also  observed 
purpura  as  a  sequel. of  scarlatina  and  measles,  as  well  as  in  the  late  course 
of  diabetes  mellitus  and  in  pulmonary  phthisis.  Bright's  disease  also  belongs 
to  those  affections  in  the  course  of  which  cutaneous  hemorrhages  occasionally 
occur.  Evidently  the  conditions  are  here  somewhat  more  complicated.  I 
should  like  to  refer  to  Mathieu's  view  that  the  purpura  which  is  seen  quite 
frequently  in  Bright's  disease  is  of  vital  importance,  and  develops  under  the 
same  conditions  as  uremia.  We  must  recognize  the  absolute  untenability  of 
this  assumption.  Purpura  arises  in  all  forms  of  nephritis,  but  especially  in 
interstitial  nephritis;  during  the  course  of  the  latter  it  often  recurs  (a  few 
spots  or  a  great  many),  and  again  disappears  without  being  of  decisive 
importance  in  prognosis. 

I  shall  revert  later  to  the  views  of  Bamberger,  a  very  careful  observer,  but 
here  I  may  mention  my  own  opinion  based  upon  numerous  observations.  Pur- 
pura and  renal  affections  appear  to  me  to  bear  double  and  varying  relation- 
ship. The  evidence  of  this  is  the  fact  that  after  long  continued,  frequently 
relapsing  purpura,  we  often  observe  albuminuria  (usually  not  exceeding  0.1 
per  cent.)  with  or  without  a  very  scant  number  of  casts.  After  a  shorter 
or  longer  duration  these  signs  gradually  disappear  without  developing  into 
chronic  nephritis.  In  a  second  group  of  cases  the  relation  is  unquestionably 
the  opposite,  inasmuch  as  with  a  contracted  kidney,  repeated  attacks  of  sim- 
ple or  hemorrhagic  purpura  occur.  But  in  such  cases  the  prognosis  does  not 
assume  a  more  serious  character. 

Dohrn  once  observed  a  child  born  of  a  woman  suffering  from  purpura,  the 
child  also  being  attacked  by  the  disease.  If  this  was  not  really  a  case  of 
hemorrhagic  diathesis  as  a  result  of  septic  infection,  the  conclusion  is  justified 
that  the  vascular  system  (blood  and  vessels)  of  mother  and  child  suffered  from 
the  same  deleterious  influences. 

In  conclusion,  we  must  mention  that  in  individual  cases  as  an  immediate 
consequence  of  severe  nervous  shock,  pain,  fright  and  fear,  severe  cases  of 
purpura  arise.     In  this  connection  I  shall  mention  the  case  of  Lebreton,  who 


MORBUS  MACULOSUS  WERLHOFII  469 

saw  purpura  in  a  young  girl  after  great  fright,  appearing  very  acutely  and 
rapidly  running  a  fatal  course.  Upon  the  skin,  large,  confluent  hemorrhagic 
spots  were  found. 

Bobrizki  saw  in  a  girl  aged  twelve,  as  the  result  of  severe  nervous  shock 
(an  attempted  rape),  an  immediate  attack  of  morbus  maculosus.  The  same 
observer  noted  a  second  case  in  a  boy  aged  ten,  who,  in  consequence  of  a 
fire,  was  severely  frightened  and  was  immediately  attacked  by  the  same  disease. 

Bobrizki  is  of  the  opinion  that  the  irritation  of  the  nervous  centers  produced 
by  fright  caused  a  paralysis  of  the  vasomotor  nerves  which  permitted  the 
extravasation  of  blood  per  diapedesin. 

GENERAL   CLINICAL  PICTURE 

By  purpura  we  understand  an  affection  which  appears  spontaneously,  it- 
chief  characteristic  consisting  in  transitory  hemorrhages  of  the  external  skin, 
the  serous  and  mucous  membranes,  as  well  as  hemorrhage  into  the  parenchyma 
of  the  internal  organs. 

Under  purpura  we  include  only  such  hemorrhages  as  denote  the  character 
of  the  disease  and  stamp  it  as  an  independent  affection,  while  the  purely 
symptomatic  extravasations  of  blood  which  occasionally  occur  in  the  course 
of  cachectic  or  febrile  affections  (as,  for  example,  in  the  course  of  sepsis  or 
acute  articular  rheumatism)  are  to  be  left  entirely  out  of  consideration.  The 
first  form  of  the  disease,  in  which  bleeding  occurs  exclusively  in  the  skin,  is' 
designated  "purpura  simplex."  When  bleeding  occurs  not  only  in  the  skin 
but  in  the  mucous  membranes,  the  serous  membranes,  and  the  internal  (paren- 
chymatous) organs  it  is  designated  purpura  hemorrhagica.  Finally,  when  the 
hemorrhages  run  their  course  with  pain  and  swelling  in  the  joints,  the  disease 
is  called  poliosis  or  purpurn  rheumatica.  This  terminology  might  be  extended 
much  further.  According  to  the  etiology  or  clinical  symptoms,  we  might  speak 
of  poliosis  or  purpura  gonorrhoica  or  of  a  purpurn  abdominalis  or  dyspeptica 
(gee  below).  But,  as  has  already  Keen  stated,  all  these  apparently  different 
forms  depend  upon  a  general  cause,  the  so-called  hemorrhagic  diathesis,  which 
is  probably  due  to  a  microparasitic  pathogenic  agent  (up  to  the  present  time 
entirely  unknown)  and  which  finds  expression  In  forms  that  are  only  clinically 
different  and  merge  into  each  other  in  many  ways.  Altogether  they  form 
one  and  the  same  essential  hemorrhagic  disease  of  varying  grade  and  varying 
intensity.  But  it  must  be  always  remembered  that,  besides  the  hemorrhagic 
symptom-,  no  other  primary  affection  is  present  in  the  clinical  picture.  Pur- 
pura simplex  La  to  be  looked  upon  as  the  mildest  form  of  the  disease;  we  can. 

however,  üever  premise  With  certainty  whether  it   will   remain   mild  during  the 

entire  course  of  the  disease,  or  will  change  gradually  into  severe  purpurn  hem- 
orrhagica, or  whether  disease  of  the  joints  or  other  complications  may  even- 
tually appear.  For  this  reason  we  cannot  look  upon  the  various  form-  of  the 
hemorrhagic  diathesis  (mentioned  by  various  authors)  as  distinct.  They  are 
all  aspects  of  one  disease,  produced  in  each  individual  case  by  separate  condi- 
tion-.    This  disease  we  call  morbus  maculosus. 

In  describing  briefly  the  history  and  development  of  this  disease,  we  need 
only  follow  a  case  Btep  by  Btep  to  demonstrate  the  difficulties  which  arise  in 


470  THE  HEMORRHAGIC  DIATHESES 

an  attempt  to  classify  these  hemorrhagic  diseases  in  accordance  with  the  usual 
reports  and  designations. 

For  example,  we  will  take  a  case  of  purpura  with  joint  affection  and  intes- 
tinal hemorrhage.  Purpura  with  joint  affection,  provided  it  is  not  also  com- 
plicated hy  intestinal  hemorrhage,  would  ordinarily  be  designated  as  peliosis 
rhcumatica.  As  most  authors  mention  neither  internal  hemorrhage  in  pelio- 
sis rheumatica  nor  joint  affections  in  purpura  hemorrhagica,  embarrassment 
would  surely  ensue  as  to  the  category  in  which  to  place  the  case  if  the  teachings 
of  these  authors  were  followed.  But  it  is  absolutely  certain  that  such  a  case 
should  be  included  in  the  great  group  of  the  hemorrhagic  diatheses. 

According  to  the  classic  descriptions  of  the  clinicians  of  the  middle  of  the 
previous  century,  it  was  generally  accepted  that  purpura  simplex,  purpura 
hemorrhagica,  and  peliosis  rheumatica  were  to  be  viewed  as  entirely  different 
diseases,  that  in  peliosis  rheumatica  no  internal  hemorrhages  occurred,  and 
further,  that  in  the  different  forms  of  purpura  no  joint  affection  was  observed. 

I  need  only  mention  here  the  revered  names  of  Eayer,  Willan,  Wunderlich, 
Schönlein,  Hebra  and  Cannstatt.  The  last,  in  complete  unanimity  with 
Wunderlich  and  Hebra,  teaches  that  in  purpura  hemorrhagica,  in  contrast  to 
peliosis  rheumatica,  no  joint  affection  occurs,  and,  moreover,  that  the  absence 
of  joint  affection  is  an  important  diagnostic  point  in  the  differentiation 
between  purpura  and  scurvy. 

A  differential  sign  between  purpura  simplex  and  purpura  hemorrhagica, 
according  to  the  previously  named  authors,  is  the  presence  of  large  ecchymoses 
upon  the  external  skin  and  the  occurrence  of  bleeding  from  the  mucous  mem- 
brane and  in  the  internal  organs  in  the  latter  affection. 

Accurate  observation  of  typical  cases  among  a  great  number  of  patients 
has  shown  the  unreliability  of  all  of  these  views,  and  has  demonstrated  espe- 
cially that  the  points  in  the  history  of  the  individual  case  regarding  the  form, 
extent  and  seat  of  the  hemorrhages,  as  well  as  in  regard  to  the  implication 
of  the  joints,  hitherto  held  to  be  diagnostic,  can  no  longer  be  so  regarded. 
As  we  shall  have  to  consider  more  minutely  these  important  questions  which 
dominate  the  situation,  I  will  only,  at  this  point,  demonstrate  by  some  typical 
examples  to  what  confusion  it  would  lead  if,  upon  the  basis  of  such  purely 
external  symptoms  and  signs,  the  cases  of  hemorrhagic  diathesis  were  to  be 
classified.  I  shall  now  show  that  other  complications  may  occur  in  hemor- 
rhagic diseases  by  which  the  external  picture  of  the  affection  may  be  appar- 
ently changed,  while  its  essential  nature  remains  the  same. 

I  shall  first  mention  two  cases  that  came  under  my  own  observation :  In 
the  first  there  were  recurring  paroxysms  of  petechia?,  large  ecchymoses  and 
suggillations  (particularly  in  the  extremities)  with  painful  arthritic  swellings, 
which  passed  rapidly  away;  besides  these,  there  were  severe  gastric  disturb- 
ances with  bilious  vomiting,  attacks  of  colic  and  recurrent  hemorrhagic  diar- 
rhea.    The  gums  were  swollen  and  bled  readily,  the  teeth  were  loosened. 

With  what  were  we  dealing?  Without  practical  experience,  it  would  be 
very  difficult  to  recognize  the  condition  among  the  earlier  classifications,  and 
we  should  lose  our  way  in  the  devious  paths  of  complicated  and  apparently 
non-related   symptom-complexes.      Purpura,   acute   rheumatic   fever,   scurvy, 


MORBUS  MACULOSUS  WERLHOFII  471 

poliosis,  dysentery,  all  these  would  be  considered,  and  formerly  would  unques- 
tionably have  been  diagnosticated. 

Yet  we  know  now,  from  careful  investigations,  that  all  of  these  symptoms, 
apparently  so  different,  may  run  side  by  side  within  the  conception  of  a 
severe  purpura. 

Which  qualifying  adjective  we  attach  to  the  purpura  in  this  case — "  rheu- 
matica,"  "  intestinalis,"  "  hemorrhagica,"  or  perhaps,  on  account  of  the  im- 
plication of  the  gums,  "scorbutica" — is  quite  immaterial;  now  one,  now 
another  symptom-group  may  assume  greater  prominence  among  the  phenom- 
ena. As  we  shall  see,  however,  all  of  the  symptoms  which  have  been  men- 
tioned may,  and  occasionally  do.  appear  in  purpura. 

The  second  case  also  is  a  characteristic  example  of  the  diagnostic  difficulties 
which  may  arise  under  some  circumstances.  Besides  the  extensive  cutaneous 
hemorrhages  which  were  of  paramount  interest,  there  were  repeated  multiple 
and  painful  joint  swellings,  appearing  and  disappearing  suddenly,  and  re- 
lapses  which  almost  always  occurred  if  the  patient  attempted  to  leave  the 
bed.  Symptoms  on  the  part  of  the  digestive  apparatus,  colic,  bilious  and 
hemorrhagic  vomiting,  and  hemorrhagic  diarrhea  were  also  present.  There 
can  be  no  doubt  that  the  case  was  one  of  so-called  purpura  rheumatica. 

is  with  extensive  cutaneous  hemorrhages  and  multiple  arthritic  affec- 
tions are  often  described  in  literature  as  "anomalous"  articular  rheumatism. 
Occasionally  these  are  combined  with  inflammation  of  the  serous  membranes, 
particularly  with  pericardial  exudates  presumably  of  a  hemorrhagic  nature. 
A  conspicuous  feature  of  these  cases  is  that  the  joint  affection  runs  a  more 
rapid  and  more  favorable  course  than  it  ordinarily  does  in  pure  acute  articular 
rheumatism.  As  similar  cases  originated  during  the  period  when  the  favor- 
able action  of  salicylic  acid  and  its  salts  upon  diseased  joints  was  unknown, 
it  mu.-t  be  suspected  that  the  authors  in  question  failed  to  recognize  the  much 
more  rapid  and  more  favorable  course  of  the  arthritic  affections  in  purpura. 
This  should  have  attracted  their  attention  to  the  fad  that  they  were  not 
(h;iling  with  genuine  articular  rheumatism  "with  an  atypical  course,"  but 
with  a  complication  of  purpura. 

Another  complication  of  purpura  which   met    with   tardy  recognition   ex- 
hibits phenomena  on  the  pari  of  the  stomach  and  intestines,  Buch  as  im 
colicky  attacks  with  vomiting  and  hemorrhagic  diarrhea. 

The  simplest  and  mildest  forms  of  pur/mm  are  those  in  which  isolated 
hemorrhagic  spots  frequently  appear  in  the  form  of  minute  petechia'  upon 
the  surface  of  the  akin  and  are  the  only  clinical  symptom.  These  sometimes 
occur  \erv  suddenly  without  being  preceded  by  prodromes.  More  often  this 
eruption  [g  accompanied  by  gastric  disturbance,  loss  of  appetite,  epigastric 
pressure,  lassitude,  vomiting  and  Blighi  fever.  The  affection  sometimes  Lasts 
but  a  few  hours,  sometimes  for  a  few  «lav-,  and.  exceptionally,  from  one  bo 
two  weeks.     The  cutaneous  hemorrhages  usually  presenl   themselves  in  the 

form   of   numerous   -mall   and    large  dusky    red   or   bluish    red   circular   -pot-; 

they  appear  particularly  upon  the  lower  h"_r-  and  feet,  often  also  upon  the 
abdomen  and  the  arm-,  and  frequently  exhausl  themselves  in  a  single  crop. 
In  fresh  cases,  they  do  no!  disappear  upon  pressure  with  the  finger,  and  they 


472  THE  HEMORRHAGIC  DIATHESES 

differ  from  flea-bites  by  the  absence  of  the  circumscribed  circular  areola, 
which  is  only  seen  in  acute  cases  and  soon  disappears.  The  face  almost  always 
remains  entirely  exempt.  Upon  the  extremities  the  extensor  areas  are  invari- 
ably more  markedly  implicated  than  the  flexor  areas.  In  form  and  size  these 
cutaneous  hemorrhages  usually  resemble  petechia?,  i.  e.,  they  are  of  the  circum- 
ference of  the  head  of  a  pin.  Occasionally  isolated,  more  extensive  hemor- 
rhages are  observed,  which  are  scarcely  larger  than  a  pea.  In  a  short  time  the 
hemorrhages  change  their  color,  and  undergo  the  well-known  alterations  in 
color  of  extravasated  hemoglobin,  or  may  cease  quite  suddenly,  without  leaving 
any  pigmentation.  After  a  few  days  at  the  longest,  during  which  time  relapses 
frequently  occur,  they  become  pale  and  disappear,  and  the  disease  may  be 
looked  upon  as  having  run  its  course.  The  patients,  who  are  sometimes  a 
little  anemic,  convalesce  and  the  disease  terminates  in  complete  restoration  to 
health;  or  one  or  several  relapses  of  the  same  mild  nature  may  occur.  Never- 
theless, after  the  process  has  run  its  course  upon  the  skin,  it  is  well  to  make 
regular  and  careful  examinations  of  the  urine  for  albumin. 

The  disease  designated  as  purpura  hemorrhagica  represents  a  severe  and 
tenacious  type  in  which,  besides  cutaneous  hemorrhages,  bleeding  also  occurs 
into  the  mucous  membranes.  This  variety  may  also  develop  without  pro- 
dromes, and  run  an  afebrile  course.  It  differs  from  the  previously  described 
form,  above  all,  by  the  fact  that  the  hemorrhages  are  more  profuse  and  more 
extensive,  so  that  the  body  looks  as  if  it  had  been  sprinkled  with  blood.  Be- 
sides punctiform  hemorrhages,  extensive  suggillations  occur  which  sometimes 
reach  as  deep  as  the  cutis,  forming  hard  infiltrations.  Sometimes  large  con- 
fluent blood  spots,  sometimes  streaks  and  globular  or  concentric  figures,  or 
confluent  masses  of  irregular  arrangement,  are  noted.  Thus  large  areas,  or 
the  greater  part  of  the  entire  cutaneous  surface,  may  be  implicated  so  that 
only  small  patches  of  skin  between  the  hemorrhagic  spots  remain  entirely 
free.  The  deeply  situated  striae-like  hemorrhages,  over  which  the  skin  shows 
all  the  colors  of  the  rainbow,  are  very  characteristic.  These  are  frequently 
found  in  the  popliteal  space,  also  upon  the  upper  arm  and  thighs,  occasionally 
upon  the  buttocks,  and  give  the  impression,  by  their  yellowish  green  or  bluish 
red  color,  that  they  were  produced  by  a  blow,  a  fall,  or  a  contusion. 

Similar  discolored  cutaneous  areas  are  found  in  scurvy  due  to  deeply-seated 
extravasations  which  have  undergone  the  same  changes  in  color  that  extrava- 
sated hemoglobin  shows.  These  extravasations  may  be  deeply  situated  in  the 
muscles  and  cause  decided  hematomata. 

Fever  may  be  entirely  absent;  if  evening  rises  in  temperature  occur  they 
are  usually  slight,  the  temperature  rarely  exceeding  101.3°  F.;  more  fre- 
quently, however,  this  form  runs  its  course  without  fever.  Occasionally,  but 
by  no  means  always,  hemorrhages  take  place  in  the  mucous  membranes.  The 
earliest  are  in  the  nasal  mucous  membrane,  and  may  produce  more  or  less 
severe  epistaxis. 

This  is  followed  by  hemorrhages  of  the  mucous  membranes  of  the  lips, 
cheeks,  palate,  and  gums,  without,  however,  as  in  the  case  of  scurvy,  giving 
rise  to  loosening  of  the  teeth  or  to  ulcerative  processes  in  the  gums;  yet  occa- 
sionally there  is  a  loosening  or  swelling  of  the  gums  and  also  even  hemorrhage. 


MORBUS  MACULOSUS  WERLHOFII  473 

Severe  gastric  conditions,  or  decided  pain  and  swelling  of  the  joints  are  more 
rarely  noted,  at  most  in  40  per  cent,  of  the  eases.  But  the  process  may  last 
a  long  time  (six  to  fifteen  months)  owing  to  repeated  relapses,  and  may  cause 
great  debility.  Severe  grades  of  anemia  combined  with  palpitation,  vertigo 
and  syncope  are  not  infrequently  observed  in  such  cases. 

The  debility  is  markedly  increased  when  the  disease  runs  its  course  with 
fever  and  albuminuria.  It  is  to  be  mentioned  that  in  bed-ridden  patients  re- 
lapses take  place  as  soon  as  the  patients  attempt  to  leave  the  bed;  it  is  at  this 
time  also  that  joint  affections  are  apt  to  appear  or  recur.  The  severe  cases  of 
purpura  hemorrhagica  with  gastric  symptoms  will  be  considered  later  on. 

Purpurn  urticans  has  been  described  by  authors  as  a  special  variety  in 
which,  besides  cutaneous  hemorrhage,  there  is  an  urticarial  eruption  of  the 
external  skin,  the  individual  wheals  of  which  appear  to  be  hemorrhagic. 
Occasionally  these  urticarial  eruptions  occur  simultaneously  with  petechias,  in 
other  cases  the  two  conditions  alternate. 

Strictly  we  should  use  the  term  "  purpura  urticans "  to  designate  only 
such  cases  of  urticaria  as  leave  behind  them  true  petechia?  or  purpuric  areas. 
I  have  observed  such  cases  in  which  each  time,  after  the  patient  had  left  his 
bed,  new  patches  of  urticaria  alternating  with  purpura  appeared,  and  in  which 
the  urticarial  eruption  invariably  left  purpuric  areas  behind.  Such  cases  last 
for  many  weeks,  or  even  for  months.  Gastric  symptoms  are  often  present  in 
purpura  urticans,  as  in  true  urticaria. 

The  forms  of  purpura  which  I  have  described  thus  far  (including  the 
milder  forms  of  the  so-called  erythema  nodosum — boil-like,  deep  infiltrations 
with  hemorrhages)  usually  appear  without  conspicuous  prodromata,  and  with- 
out other  local  disturbances.  In  contrast  with  these  forms  of  "  pure  "  purpura 
are  others  in  which,  a  few  days  prior  to  the  appearance  of  the  hemorrhagic 
phenomena,  mild  prodromes  of  an  indefinite  nature,  lassitude,  headache,  an- 
orexia, may  be  observed.  Finally  a  drawing  sensation  in  the  Limbs  and  pain 
in  the  joints  may  usher  in  the  malady;  then  moderate  \'r\c]\  lasting  several 
days,  with  pain  in  the  joints,  particularly  of  the  lower  extremity,  appear  and 
last  until  the  outbreak  of  the  true  purpuric  affection.  Thus  we  reach  the 
form  which  has  been  designated  peliosis  or  purpura  rheumatica.  It  is  to 
Schönlein's  credit  thai  he  firsl  recognized  the  unquestionable  and  intimate 
relation  existing  between  the  hemorrhagic  diathesis  and  certain  arthritic  affec- 
tions; Imi  lie  did  nol  discern  thai  this  connection  is  a  very  general  one.  On 
the  contrary,  he  declared  it  t<>  be  only  a  limited  one,  and  thus  he  failed  t<> 
apprehend  the  true  nature  of  the  hemorrhagic  diathesis,  the  proper  under- 
standing of  which  was  delayed  for  a  long  time. 

The  designation  peliosis  (rj  7rcAiWi<»  )  is  fir-t  found  in  tin1  werk-  of 
Hippocrates  and  Bignifies  "blood  under  the  skin."  A-  is  well  known.  Sch.'m- 
lein  appropriated  this  term  a-  a  designation  for  the  clinical  picture,  and  added 
to  it  the  epithel  "  rheumatica." 

According  t<>  Schönlein'e  well  known  lectures,  which  were  published  by 

me  of  hi-  pupils."  the  following  are  the  main  symptoms  of  peliosis  rheu- 
matica: "The  areas  never  coalesce.  The  patient-  have  either  formerly  suf- 
fered from  rheumatism,  or  then  exhibil  rheumatic  phenomena,  mild  periodic 


474  THE  HEMORRHAGIC  DIATHESES 

pains  in  the  joints  (in  the  ankles,  in  the  knees,  or  in  the  joints  of  the  hand 
and  shoulder).  These  joints  are  edematous  and  painful  to  the  touch.  The 
spots  characteristic  of  the  disease  appear  in  the  majority  of  cases  first  upon 
the  extremities,  particularly  upon  the  lower,  and  then  only  up  to  the  knees. 
The  hemorrhagic  areas  are  of  the  size  of  a  lentil  or  a  millet-seed,  light  red, 
not  raised  above  the  skin,  and  gradually  turn  a  dirty  brown  and  desquamate. 
(The  latter  symptom  in  my  experience  is  most  often  absent!)  The  eruption 
occurs  in  crops  during  a  period  lasting  often  for  weeks.  Any  change  of 
temperature,  no  matter  how  slight,  may  cause  a  new  eruption.  The  affection 
is  mostly  accompanied  by  fever,  which  is  of  the  remittent  type. 

"  The  disease  has  been  confounded  with  morbus  maculosus  Werlhofii.  The 
absence  of  the  so-called  purpuric  phenomena  in  the  mouth  which  shows  no 
changes,  the  absence  of  free  hemorrhages,  the  absence  of  nervous  phenomena, 
the  character  of  the  exanthem  (never  reaching  the  size  typical  of  Werlhof's 
disease,  never  becoming  confluent,  and  being  a  light  red),  the  affection  of  the 
joints  which  is  lacking  in  maculosus,  the  great  debility  and  loss  of  strength, 
confirm  the  diagnosis. 

"  The  clinical  picture  is  seen  in  individuals  with  a  delicate,  vulnerable  skin, 
who  have  either  previously  suffered  from  rheumatism  or  in  whom,  as  the 
result  of  chilling,  symptoms  of  peliosis  simultaneously  with  those  of  rheuma- 
tism appear."     So  much  for  Schönlein's  view. 

Notwithstanding  the  great  master's  beautiful  and  exact  portrayal  of  the 
clinical  picture  which  has  been  named  after  him,  it  is  evident  that  his  experi- 
ence in  purpuric  diseases  was  not  extensive.  We  find  in  this  description  all 
the  errors  which  have  so  long  dominated  this  department  of  clinical  medicine ; 
they  have  been  propagated  in  the  text-books  for  three  decades,  and  have 
retarded  the  recognition  of  the  true  nature  of  this  group  of  diseases. 

Particularly  fallacious  is  the  idea  that  the  situation  and  the  size,  as  well 
as  the  configuration  of  the  hemorrhages,  are  characteristic  of  this  or  that 
form,  as  well  as  the  isolation  or  the  confluence  of  the  purpuric  spots.  It  is 
equally  unimportant  whether  the  hemorrhages  occur  only  upon  the  external 
skin  or  also  upon  the  mucous  membranes.  But  the  erroneous  interpretation 
of  the  presence  or  absence  of  arthritic  affections  in  the  hemorrhagic  diathesis 
had  more  influence  than  any  other  factor  in  preventing  a  true  understanding 
of  the  nature  of  the  malady.  The  recognition  of  the  fact  that  in  every  form  of 
the  hemorrhagic  diathesis  the  joints  may  be  implicated  did  not  come  till  much 
later.  The  correction  of  this  error  may  properly  be  looked  upon  as  the  most 
important  advance  in  the  knowledge  of  the  hemorrhagic  diseases. 

Literature  furnishes  but  a  single  autopsy  report  of  the  disease  described 
under  the  misleading  term  peliosis  rheumatica.  This  case  is  from  Traube's 
Clinic,  and  is  reported  by  Leuthold.  It  deserves  special  consideration,  because 
Traube  was  for  a  long  time  Schönlein's  clinical  assistant,  and  knew  exactly 
what  Schönlein  meant  by  the  designation  "  peliosis  rheumatica."  The  case  is 
briefly  as  follows :  A  carpenter,  aged  thirty-nine,  after  prolonged  lifting  in  the 
Clinic,  developed  slight  pain  in  the  joints.  There  was  edema  of  the  feet,  and 
upon  the  dorsum  of  both  several  small  dark  red  areas  about  the  size  of  a 
pin's  head  appeared;  these  areas  did  not  rise  above  the  level  of  the  skin  nor 


MORBUS  MACULOSUS  WERLHOFII  475 

disappear  upon  pressure  with  the  finger.  At  the  malleoli  (which,  like  all  the 
joints  of  the  feet,  were  particularly  tender  to  the  touch)  there  were  areas  of 
the  same  kind  but  of  larger  circumference.  The  temperature  rose.  A  few 
days  later  there  was  distinct  swelling  in  the  right  knee-joint ;  in  the  following 
night  there  were  tearing  pains  in  the  joint  and  a  further  eruption  of  petechias, 
which  was  most  profuse  upon  the  forearm  and  lower  extremity,  occurred  in 
groups  or  isolated  in  parts  of  the  body  excepting  the  thorax  and  the  face. 
Besides  this,  marked  edema  of  the  hands  and  erythema  of  the  finger-joints 
developed ;  in  the  same  region  after  the  appearance  of  petechias  in  the  following 
night  with  swelling  of  the  left  knee-joint,  large  extravasations  of  blood  oc- 
curred, raising  the  skin  in  the  form  of  tense  vesicles. 

While  some  of  the  petechias  became  pale  and  disappeared,  new  crops  of 
hemorrhagic  patches  appeared  simultaneously  with  an  improvement  in  the 
arthritic  swelling.  The  fever  during  this  time  was  partly  of  the  continued 
and  partly  of  the  intermittent  type.  Albuminuria  was  present.  Among  the 
autopsy  findings  I  shall  only  mention  those  of  the  diseased  joints :  In  the  right 
knee-joint,  which  was  somewhat  distended,  much  colorless,  viscid,  ropy  fluid; 
the  synovial  membrane  very  pale,  only  in  isolated  areas  in  the  upper  part  here 
and  there  brownish  points.  The  fatty  areas  show  decided  injection.  The 
semilunar  cartilage  is  transparent,  somewhat  yellowish  upon  the  border.  In 
the  left  knee-joint  also  much  clear  fluid  and  around  the  patella  fenestration, 
transudation  and  vascular  injection;  under  the  tendon  of  the  extensor  of  the 
knee,  brownish  extravasations,  partly  fresh,  partly  fading. 

"  The  pathologico-anatomical  findings  in  this  obscure  process  which  Schön- 
lein has  described  as  poliosis  rheumatica,  differ  in  no  respect  from  the  changes 
shown  at  autopsy  in  the  joints  in  acute  rheumatism."  Xear  this  the  impor- 
tant note  is  found:  "Not  markedly  different  from  the  findings  in  gonor- 
rheal rheumatism." 

A  patient  in  the  course  of  gonorrhea  was  attacked  by  ileotyphus,  which 
caused  death  at  the  beginning  of  the  eighth  day.  In  the  autopsy  report  the 
following  is  noted  :  ->  Tbc  right  knee  is  perhaps  somewhat  wider  than  the  left 
externally;  otherwise  very  little  that  is  abnormal.  Internally  there  was  a  vrery 
marked,  fine,  dark-red  injection  of  the  ligamenta  cruciata,  as  well  as  of  the 
entire  capsule  of  the  joint,  besides  a  gelatinous  edema  of  the  same,  most 
developed  around  the  patella.  The  cartilage  of  the  joint  and  the  semilunar 
cartilage  present  nothing  abnormal.  The  fluid  in  the  joint  is  Bcant,  some- 
what more  viscid  and  darker  than  normal.  In  their  sequelae  also,  genuine 
rheumatism  and  gonorrhea]  rheumatism  appear  to  have  a  certain  similarity, 
as  may  be  noted  from  the  observation  of  an  endocarditis,  which  occurred  in 
connection  with  the  rheumatism  of  a  Long-existing  gonorrhea,  and,  therefore, 
must  be  Looked  upon  as  dependent  upon  it." 

Thus  far  the  fact-!  Whether  or  not  we  recognize  the  existence  of  a  clin- 
ical picture  -ucb  as  Schönlein  described  and  designated  as  peliosis  rheumatica 
must  be  Left   to  the  individual  judgment     Probably  all   will  agree  on  one 

point,  viz.  :  that  if  we  adopt  the  name  introduced  by  Schönlein  we  must  under- 
stand by  it  what  he  understood.  Nevertheless  we  frequently  find  the  name 
used  without  any  clinical  picture  in  the  remotest  degree  resembling  the  condi- 


476  THE    HEMORRHAGIC   DIATHESES 

tion  described  by  Schönlein.  I  shall  mention  here  only  the  well-known  cases 
of  Bamberger,1  the  description  of  which  the  author  introduces  with  the  words : 
"  The  so-called  peliosis  rheumatica  in  the  lower  extremities  often  occurs  in 
Bright's  disease.  I  find  five  cases  of  this  kind  among  my  observations.  Usu- 
ally the  purpuric  areas  remain  unchanged  for  many  months.  What  connec- 
tion exists  here,  if  we  do  not  use  general  expressions,  is  not  at  present  clear. 
In  two  instances  an  autopsy  was  held :  I  shall  briefly  describe  the  cases : 

"  1.  A  man  aged  thirty-nine,  always  well,  admitted  to  the  hospital  on  ac- 
count of  pain  and  hemorrhagic  areas  upon  the  lower  extremities.  After  some 
days  edema;  great  amount  of  albumin.  Pleurisy.  Death.  At  the  autopsy 
hemorrhages  were  found  in  the  skin,  upon  the  mucous  membrane  of  the  stom- 
ach, and  in  the  kidneys. 

"2.  A  woman  aged  thirty-six.  Besides  the  usual  symptoms  of  Bright's  dis- 
ease, there  was  stenosis  of  the  mitral  valve,  also  engorgement  of  the  liver. 
Purpuric  areas  upcn  the  lower  extremity  had  existed  over  a  year.  Death  due 
to  apoplexy.  Autopsy.  Fresh  hemorrhagic  focus  in  the  brain;  stenosis  of 
the  mitral  valve ;  wedge-shaped  infarct  in  the  spleen ;  pneumonia  and  chronic 
nephritis." 

These  cases  do  not  in  the  least  resemble  the  clinical  picture  of  Schönlein; 
in  each  case  he  was  dealing  with  a  chronic  nephritis  with  purpura  the  result 
of  cachexia  and  the  hemorrhagic  diathesis  due  to  this  (peliosis  cachecticorum). 
Bamberger  here  uses  the  designation  "  peliosis  "  as  synonymous  with  "  pur- 
pura," and  has  no  reason  to  speak  of  a  rheumatic  form  as  he  in  no  way  indi- 
cates any  disease  of  the  joints.  If  one  searches  for  the  etiologic  relationship 
of  the  symptoms,  one  must  surely  find  it  in  the  loss  of  albumin  which  caused 
the  cachexia,  and  in  the  hemorrhagic  diathesis  dependent  upon  this. 

I  have  seen  great  numbers  of  cases  with  hemorrhages  such  as  Bamberger 
described,  in  chronic  nephritis  as  well  as  also  in  old  valvular  lesions  of  the 
heart,  and  have  only  here  described  these  in  order  to  show  that  the  clinical 
picture  presented  by  prominent  clinicians  a  comparatively  short  time  after 
Schönlein's  teaching  was  so  obscured  that  nothing  was  left  of  it  but  a  pecul- 
iar type  of  cutaneous  hemorrhage.  That  this  has  been  generally  looked  upon 
as  the  main  symptom  of  the  affection  is  shown  by  an  examination  of  the 
literature.  Here  we  are  forcibly  impressed  with  the  fact  that,  step  by  step, 
from  the  great  group  of  purpura  varieties  which  ran  their  course  with  arthritic 
symptoms,  one  particular  form  was  arbitrarily  separated  and  presented  as  an 
independent  disease.  As  the  number  of  cases  accumulated  it  became  clearer 
that  arthritic  affections  may  occur,  and  do  occur  in  every  variety  of  hemor- 
rhagic disease.  Soon,  without  an  exception,  all  those  cases  were  described  as 
peliosis  rheumatica  in  which  the  two  symptoms  were  found.  If  the  cases  hap- 
pened to  differ  very  widely  from  Schönlein's  description  they  were  explained  as 
a  form  of  peliosis  with  "  an  atypical  course."  Thus  it  came  to  pass  that  nei- 
ther a  definite  form  of  hemorrhage  nor  any  special  type  of  joint  affection  was 
considered  typical  of  the  clinical  picture  in  question,  and  on  the  other  hand  no 
importance  was  attached  to  etiology. 

i  Würzburger  med.  Zeitschr.,  Bd.  i,  1860. 


MORBUS  MACULOSUS  WERLHOFII  477 

In  consequence  of  these  slovenly  methods  of  classification  cases  of  ulcera- 
tive endocarditis  with  purulent  arthritis  and  multiple  cutaneous  and  internal 
hemorrhages  finally  came  to  be  designated  as  peliosis  rheumatica,  and  hemor- 
rhage in  the  latter  disease  was  assumed  to  be  embolic.  But  if  we  leave  out 
of  consideration  altogether  the  results  of  these  blunder-,  vre  find  in  literature 
an  increasing  number  of  cases  described  as  peliosis  rheumatica  which  have 
nothing  in  common  with  the  original  Schönlein  clinical  picture  except  the 
combination  of  hemorrhages  and  joint  affection.  Attention  to  a  particular 
type  of  hemorrhage  soon  ceased,  and  instead  of  the  isolated,  non-confluent, 
lentil-sized  petechias  upon  the  lower  extremities,  described  by  Schönlein,  we 
find  writers  including  in  their  descriptions  every  form  of  cutaneous  hemor- 
rhage, of  mucous  membrane  hemorrhage,  and  of  hemorrhage  into  internal 
organs.  If  we  attempt  to  bring  order  out  of  the  chaos  of  pathologic  entities 
and  clinical  pictures  described  in  literature  under  the  name  of  peliosis  rheu- 
matica we  find  simple  purpura,  purpura  hemorrhagica  and  purpura  urticans, 
morbus  maculosus  Werlhofii,  scurvy,  true  peliosis  rheumatica  and,  finally, 
erythema  nodosum. 

Occasionally  we  find  each  of  these  maladies,  running  their  course  with 
cutaneous  hemorrhage,  complicated  with  joint  affections,  as  will  be  later  ex- 
plained in  detail.  Hence  the  decision  as  to  the  nature  and  character  of  the 
disease  should  not  depend  upon  the  Beat,  nor  the  size,  nor  the  form  and  conflu- 
ence of  the  hemorrhages,  nor  upon  the  implication  of  the  mucous  membranes, 
the  serous  membranes  or  the  internal  organs,  nor  even  upon  the  sequence  of 
the  individual  symptoms,  but  wholly  upon  the  etiology.  This,  however,  in  the 
group  of  diseases  above  mentioned,  must  be  Looked  for  in  those  change-  in  the 
blood  which  we  have  designated  by  the  term  hemorrhagic  diathesis.  Patients 
suffering  from  this  disease  have  a  pale,  delicate  skin  which  upon  the  slightest 
cause  Bhows  a  tendency  to  hemorrhage;  they  also  present  the  well-known  symp- 
toms of  chlorosis  and  anemia.  It  is  probably  due  to  this  vulnerability  of  the 
skin,  which  is  also  unusually  sensitive  to  change-  in  temperature,  that  such 
individuals  are  more  readily  attacked  by  rheumatoid  affections  than  others. 
It  seems  arbitrary  to  isolate  from  this  great  complex  of  cases  which  have  a 
common  cause,  a  single  group  particularly  characterized  by  the  behavior  and 
localization  of  the  petechia?,  and  to  assign  a  particular  name  to  it.  Tn  any 
Large  hatch  of  clinical  material  many  cases  will  be  met  with  which  correspond 
minutely  to  the  description  of  Schönlein,  with  the  sole  difference  that  the 
form  of  the  hemorrhages  varies,  or  that  they  have  their  -eat  in  the  mucous 
membranes.  How  can  the  latter  be  reasonably  described  a-  peliosis  rheu- 
matica. and  the  former  not  ?  I  have  a  large  number  of  clinical  histories  which 
I  have  been  for  a  long  lime  collecting  because  I  was  interested  in  the  ques- 
tion of  ihr  relation  between  the  hemorrhagic  diseases  and  affection  of  the 
joints.     I  -Im  1 1  refer  later  to  the  conclusions  based  on  these,  and  at  this  point 

shall    only   -tale  that    I    concur   in    the  opinion    at    which    Scheby-Buch    arrived 

after  careful  study:  "The  history  of  peliosis  rheumatica  is  of  itself  sufficienl 
to  show  the  untenability  of  the  view  that  it  i-  an  independent  disease,  even  if 
we  did  not  have  other  weighty  reasons  for  the  same  conclusion." 

No  one  would  think  of  designating  -curvy  combined  with  arthritic  affec- 


478  THE  HEMORRHAGIC  DIATHESES 

tion  as  peliosis  rheumatica,  yet  carefully  studied  cases  of  purpura  hemor- 
rhagica with  joint  affection  have  been  described  by  some  writers  as  peliosis 
rheumatica,  and  by  others  as  acute  articular  rheumatism  with  hemorrhages. 
French  and  English  authors  were  among  the  first  to  describe  all  such  cases  of 
extensive  hemorrhagic  diathesis  with  articular  affection  as  "  acute  articular 
rheumatism  with  atypical  course"  and  thus  to  a  certain  extent  constructed  a 
new  clinical  picture.  This  example  shows  what  the  results  might  be  if,  with- 
out the  protective  guidance  of  etiology,  and  solely  on  the  basis  of  obvious 
symptoms,  one  should  attempt  to  classify  these  cases !  With  a  sharply  defined 
clinical  picture  such  as  scurvy  usually  presents,  only  an  unusually  slovenly 
habit  of  mind  could  make  it  possible  to  mistake  the  relation  of  the  symptoms. 
But  the  case  is  quite  different  when  we  attempt  to  deal  with  the  group  of  cases 
last  indicated.  Some  authors  describe  them  as  purpura  or  peliosis  rheumatica, 
according  to  whether  the  cutaneous  phenomena  or  the  joint  affections  are 
more  prominent;  others  call  them  rheumarthritis,  without  realizing  that  the 
clinical  picture  does  not  correspond  to  Schönlein's  conception,  and  that  in 
acute  articular  rheumatism  cutaneous  hemorrhages  do  not  occur  except  in  the 
presence  of  certain  severe  complications  ! 

One  who  has  seen  much  of  acute  articular  rheumatism  knows  that  it  has 
in  uncomplicated  cases  no  association  with  cutaneous  hemorrhages,  and  will 
not  confound  this  disease  with  any  other.  Of  great  importance  is  the  tend- 
ency of  rheumatism  to  produce  secondary  inflammations  of  the  serous  mem- 
branes and  of  the  endocardium,  which  is  absent  or  extremely  rare  in  the  pure 
form  of  peliosis  and  in  the  hemorrhagic  diathesis.  Further,  the  absence  in 
all  forms  of  purpura  of  the  very  severe  and  exhausting  sweats  of  acute  rheu- 
matism, as  well  as  the  absence  of  severe  joint  phenomena,  is  important.  Cuta- 
neous or  internal  hemorrhages  (particularly  of  the  retina)  occurring  in  acute 
rheumatism  depend  upon  a  complicating  acute  endocarditis,  as  I  have  explic- 
itly pointed  out  in  my  monograph  upon  septic  diseases.1  Such  cases  are  also 
to  be  clearly  differentiated  from  those  in  which,  with  a  simultaneous  septic 
or  so-called  ulcerative  endocarditis,  purulent  joint  metastases  with  numerous 
petechia?  distributed  over  the  entire  skin  and  retinal  hemorrhages  appear. 
The  cardinal  difference  between  these  groups  is  that,  in  the  former,  acute  artic- 
ular rheumatism  introduces  the  scene  and  represents  the  original  disease,  while 
in  the  latter  a  wound  affection  (for  example,  diphtheria  of  the  placental  area, 
etc.)  or  internal  suppuration  (such  as  thrombophlebitis  suppurativa  of  the 
pelvic  veins  due  to  abortion,  or  of  the  spermatic  veins  in  the  course  of  gonor- 
rhea) is  the  cause.  In  the  last-named  group  of  cases  the  joint  affections  are 
invariably  secondary.  Many  examples  of  both  varieties  of  cases  have  been 
given  in  my  article  upon  septic  disease.      (See  p.  380  et  seq.,  and  p.  588.) 

Having  now  proven,  as  I  believe,  that  there  is  no  justification  for  Schön- 
lein's clinical  picture  of  peliosis  rheumatica,  and  that  the  condition  was  a  joint 
affection  combined  with  a  hemorrhagic  diathesis,  I  must  mention  that  there 
are  cases  which  run  a  course  exactly  as  described  by  Schönlein,  except  that 
they  are  due  to  another  cause,  namely,  gonorrhea.     I  have  used  the  designa- 

i  Zcitschr.  f.  Min.  Med.,  Bd.  ii,  1881. 


MORBUS   MACULOSUS  WERLHOFII  479 

tion  "poliosis  gonorrhoica"  in  my  article  upon  this  subject,1  because  I  wished 
to  point  out  to  the  profession  the  external  connection,  ami  also  that  there 
might  be  no  misunderstanding  of  what  I  mean  by  the  expression,  bul  1  shall 
not  consider  further  the  form  of  joint  affection  with  cutaneous  hemorrhage 
which  arises  in  connection  with  gonorrhea. 

In  the  main.  Schönlein's  description  is  applicahle  to  the  milder  forms  of 
rheumatic  purpura.  Some  further  explanation  will  he  given  in  the  descrip- 
tion of  the  so-called  Henoch's  purpura.  With  the  appearance  of  purpura  the 
arthritic  pains  generally  cease.  Not  infrequently  the  purpuric  spots  are  asso- 
ciated with  urticarial  eruptions  and  edema  of  the  dorsum  of  the  feet  and 
ankles,  as  well  as  with  erythema  multiforme  exsudativum.  The  disease  may 
run  its  course  in  a  few  weeks.  Frequently,  however,  relapses  occur  with  re- 
newed arthritic  pain  and  fresh  eruptions  of  purpura,  and  the  disease  some- 
times lasts  for  months,  even  from  eighteen  months  to  two  years  and  longer. 
Fever  may  be  present  or  completely  absent. 

The  more  intense  the  affection  of  the  joint  the  higher  the  evening  rise 
of  temperature.  In  very  severe  cases,  in  which  the  clinical  picture  may  re- 
semhle  acute  articular  rheumatism,  we  find  prolonged  fehrile  rises  of  a  remit- 
tent character.  The  affection  differs  from  true  typical  articular  rheumatism, 
above  all.  by  the  absence  of  profuse  sweats  and  of  a  tendency  to  endocardial 
complications,  to  which  the  hemorrhages  occasionally  seen  in  true  rheumatism 
are  to  he  referred.  Nevertheless  in  rare  and  severe  cases  of  rheumatic  pur- 
pura, the  appearance  of  the  diseased  joints  may  very  closely  resemble  that  in 
true  acute  articular  rheumatism,  even  to  such  an  extent  that  a  differentiation 
is  impossible.  In  a  ease  from  Trauhc's  Clinic  reported  by  Leuthold,  which 
ran  a  fatal  course,  the  condition  of  the  joint  differed  nowise  from  the  changes 
which  are  observed  at  the  autopsy  in  acute  rheumatism  (-er  above).  How- 
ever, no  report  of  purpura  rheumatics  is  known  to  me  in  which  a  purulent 
effusion  was  met  with  in  the  joint  cavities.  If  the  disease  is  very  much  pro- 
longed, anemic  symptoms  become  noticeable  as  in  acute  rheumatism,  among 
other.-  anemic  cardiac  murmurs.  Only  rarely  is  enlargement  of  the  spleen 
observed. 

Hemorrhages  into  the  mucous  membranes  are  not  absent;  thus  Kaposi 
found  in  one  case  hematuria,  in  another  case,  which  terminated  lethally,  ecchy- 
mosis  with  aubsequenl  gangrene  of  the  mucous  membrane  of  the  palate,  while 
Duhring  described  a  bloody  discharge  from  the  genitalia.  These  cases  resem- 
bled the  form,  now  to  he  delineated:   Henoch's  "purpura  abdominalis." 

Henoch  firsl  noted  in  the  year  L868  as  a  complication  of  purpura  the  fact 
!hat  the  eruption  of  purpura  ami  the  arthritic  phenomena  may  he  accompanied 
by  a  number  of  abdominal  Bymptoms:  Vomiting,  hemorrhagic  diarrhea  and 
colic.  Henoch  represented  a-  characteristic  the  appearance  of  these  symptoms 
in  paroxysms  with  an  interval  usually  Lasting  several  week-,  and  occasionally 

even  a-  long  a-  a  jrear.  In  the  earlier  literature  upon  purpura,  with  the  excep- 
tion of  a  case  by  Wit  tan.  there  ig  no  deli  nit  e  report  of  the  occurrence  of  tin-  dis- 
ease in  combination  with  joint  troubles  ami  Bevere  abdominal  Bymptoms.    We 

'  Dermatologisch   Zeitschrift,  \\x. 


480  THE  HEMORRHAGIC  DIATHESES 

therefore  regard  this  not  as  a  special  form  of  purpura  but  as  a  special  mani- 
festation of  the  same  transitory  hemorrhagic  diatheses  which  in  all  cases  have 
one  and  the  same  pathogenetic  cause. 

According  to  v.  Dusch  and  Hoche  the  affection  occurs  especially  in  youth. 
In  earliest  childhood,  from  the  first  to  the  third  year,  and  in  advanced  age, 
beyond  the  forty-sixth  year  of  life,  no  case  is  known;  after  the  third  year 
the  number  of  cases  gradually  increases  to  its  maximum  between  the  ninth 
and  twelfth  years.  The  frequency  then  remains  about  the  same  up  to  the 
twenty-fourth  year.     Beyond  this  age  the  affection  again  becomes  quite  rare. 

Males  are  more  frequently  attacked  than  females;  of  forty  patients  whose 
sex  is  mentioned  33  were  males  and  7  females.  These  reports  regarding  age 
and  sex  differ  decidedly  from  those  of  other  authors.  Regarding  sex,  I  have 
noted  a  decided  preponderance  of  the  affection  in  males. 

As  predisposing  causes,  besides  recovery  from  a  previous  acute  rheumatic 
attack,  unfavorable  hygienic  conditions,  damp  dwellings  and  insufficient  nutri- 
tion are  sometimes  noted,  but  among  the  cases  there  are  also  patients  who  have 
not  been  subjected  to  these  influences.  It  is  necessary  to  emphasize  this,  as 
purpura  is  still  occasionally  spoken  of  as  a  disease  of  the  proletariat,  and  as 
the  expression  of  a  certain  general  cachexia. 

With  more  or  less  disturbance  in  general  health  of  varying  duration,  accom- 
panied by  headache,  lassitude,  anorexia,  etc.,  rheumatoid  pains  appear  which 
are  drawing  or  tearing  in  character,  not  strictly  localized,  but  in  various  parts 
of  the  body,  having  their  seat  particularly  in  the  lower  extremity  and  in  the 
back.     At  times  there  is  a  transitory  edematous  swelling  in  the  affected  regions. 

Some  of  the  patients  now  take  to  bed,  others  continue  to  follow  their  ordi- 
nary pursuits.  Soon,  however,  severe  pains  occur  in  one  or  more  joints,  usu- 
ally without  any  perceptible  external  change  in  the  affected  area;  in  other 
cases  one  or  more  joints  begin  to  swell,  the  skin  reddens,  becomes  hot,  and 
in  the  surrounding  areas  edematous  infiltrations  appear,  quite  as  in  acute 
articular  rheumatism.  In  this  stage  sometimes  mild  fever  is  noted;  tempera- 
tures reaching  101.3°  F.  are  rare,  as  are  high  temperatures  in  the  later  course 
of  the  disease. 

As  a  rule,  the  pains  and  immobility  of  the  joints  cause  the  patient  to  send 
for  a  physician,  and  frequently  he  is  the  first  to  note  the  purpuric  areas,  which 
are  at  the  onset  isolated,  arising  without  any  subjective  symptoms.  Usually 
the  eruption  causes  itching  only  when  it  begins  with  urticaria.  Generally 
a  period  of  several  days  intervenes  between  the  occurrence  of  the  joint  pains 
and  the  appearance  of  the  first  eruption  of  purpura. 

The  purpura  itself,  in  the  beginning  usually  bright  red  and  consisting  of 
small,  irregular  and  isolated  spots,  or  groups  formed  of  these,  gradually 
coalesces  into  larger,  irregular  areas,  which  in  the  course  of  a  few  days  show 
a  change  in  color  and  become  bluish  or  yellow  or  dark  brown. 

From  the  lower  leg  (where  they  frequently  but  by  no  means  always  appear 
first)  they  distribute  themselves  gradually  by  continuity,  or  in  jumps  to  the 
upper  thigh,  buttocks  and  gluteal  regions.  Xew  eruptions  appear  upon  both 
arms,  or  upon  the  trunk,  so  that  sometimes  the  entire  body,  particularly  the 
region  of  the  larger  joints,  appears  covered  with  purpuric  spots. 


MORBUS  MACULOSUS  WERLHOFII  481 

While  the  pupura  itself  causes  the  patient  great  anxiety  but  does  not  actu- 
ally give  rise  to  suffering,  other  symptoms  soon  become  prominent  and  are 
much  more  troublesome,  e.  g.,  disturbances  on  the  part  of  the  intestinal  tract 
which  are  characteristic  in  that  they  generally  resist  all  treatment.  Patients 
complain  of  severe  colic-like  pains  in  the  abdomen,  particularly  in  the  umbil- 
ical region,  which  are  frequently  so  severe  as  to  bend  the  patienfs  body,  and 
evoke  loud  cries.  The  abdomen  is  also  retracted  and  sensitive  to  pressure; 
the  bowels  at  the  beginning  of  the  attack  are  constipated.  These  difficulties 
are  increased  by  a  stubborn  vomiting,  which  at  first  contains  the  food  lasl  in- 
troduced, then  consists  of  yellowish  green  bilious  masses  frequently  admixed 
with  blood.  The  pulse  becomes  small  and  rapid;  the  facial  expression  shows 
anxiety;  the  entire  condition  is  a  pitiable  one. 

The  constipation  which  is  present  at  the  onset  soon  give-  way  to  a  more 
or  less  profuse  discharge  of  thin  yellowish  feces  often  admixed  with  blood, 
the  occurrence  of  which  sometimes  coincides  with  the  cessation  of  the  pain. 

The  colic  and  the  vomiting  occasionally  last  for  days;  the  patient  eats  little 
or  nothing.  Now  and  then  under  the  influence  of  severe  retching,  epistaxis 
occurs.  Gradually  all  of  the  phenomena  ameliorate,  the  vomiting  ceasing 
first,  then  the  abdominal  pains,  while  the  thin  feeal  discharges  continue  to 
be  voided  from  time  to  time  until  the  period  of  apparent  convalescence. 

The  pains  in  the  joints  have  in  the  meantime  ceased,  and  the  purpura  has 
faded.  In  case  none  of  the  complications  which  are  to  be  described  have 
appeared,  the  patient,  aside  from  a  certain  exhaustion,  is  comparatively  well 
and  believes  that  convalescence  has  begun.  Occasionally  no  other  attack 
occurs,  and  convalescence  proceeds  uninterruptedly;  in  the  majority  of  cases. 
however,  the  symptoms  are  repeated,  wholly  or  in  part,  after  a  period  which 
may  vary  from  one  day  to  several  weeks,  until  finally  recovery  ensues.  In 
relatively  rare  cases  death  takes  place. 

Bui  a  schematic  course  such  as  described  is  not  the  rule;  in  children  the 
typical  clinical  picture  is  mosl  often  seen.  The  frequenl  deviations  and 
manifold  peculiarities  observed  in  the  course  of  most  adult  cases  can  hest  be 
explained  by  a  description  of  the  individual  symptoms. 

These  will  be  minutely  discussed  under  the  special  symptomatology,  so  that 
at  this  place  only  a  U'\v  concluding  remarks  will  be  made  concerning  this  form 
of   purpura. 

Among  the  peculiarities,  a  group  of  eases  must  be  mentioned  (rare  and 
in  part  insufficiently  described)  in  which  the  arthritic  affection  is  entirely 
absent,  and.  besides  the  purpura,  only  marked  intestinal  disturbances  exist. 

The  duration  of   Henoch"-  purpura  varies  within  wide  limits;   numerous  cases 

have  been  recorded  lasting  from  seven  days  up  to  nine  months;  as  an  average 

duration.  -i\   to  twelve   weeks  may  he  mentioned. 

The  prognosis  in  children  in  the  main  is  good  among  nineteen  cases  there 
was  hut  one  fatal  case,  and  this  was  in  consequence  of  acute  nephritis.  In 
adult-  it  is  less  favorable.  In  twenty-two  cases  recorded,  five  were  fatal. 
A  definite  opinion  cannot  be  given  on  account  of  the  paucity  of  records. 

We  now  reach  a  special  manifestation  of  the  disease,  which  was  also  de- 
Bcribed  by  Henoch  in  L881  under  the  name  of  purpura  fulminans.     I  described 


482  THE  HEMORRHAGIC  DIATHESES 

an  analogous  clinical  picture  nine  years  previously,  in  the  year  1878,  and  also 
described  it  and  pictured  it  accurately  in  1881,  without,  however,  giving  the 
condition  this  very  descriptive  name.  In  all  of  these  cases  there  is  an  ex- 
tensive cutaneous  hemorrhage  which  rapidly  leads  to  death,  of  which  Henoch 
himself  has  seen  three  cases,  while  a  fourth  was  described  in  1886  by  Charron 
in  Brussels. 

All  these  cases  have  in  common  the  feature  that  hemorrhages  upon  the 
mucous  membranes  are  wholly  absent,  but  with  great  rapidity,  extensive 
ecchymoses  appear  which,  in  a  few  hours,  change  the  entire  skin  of  the  ex- 
tremities to  blue  and  dark  red,  and  represent  a  dense  bloody  infiltration  of  the 
cutis.  The  formation  of  hemorrhagico-serous  vesicles  upon  the  skin  occurred 
in  two  cases,  but  gangrene  has  never  been  noted  and  no  fetid  odor  has  been 
observed.  The  course  is  exceedingly  rapid;  within  twenty-four  hours  after 
the  formation  of  the  first  purpura  death  occurred;  the  longest  duration  was 
four  days.  Xo  complication  was  present,  and,  with  the  exception  of  general 
anemia,  the  autopsy  showed  an  entirely  negative  condition;  there  was  no  sign 
whatever  of  embolic  or  thrombotic  processes.  One  of  Henoch's  cases  devel- 
oped two  days  after  the  crisis  in  pneumonia,  another  one  and  a  half  weeks 
after  a  very  mild  scarlatina.  In  both  of  the  other  cases,  as  well  as  in  mine, 
there  was  absolutely  no  known  etiology.  Two  analogous  cases  have  been 
since  published  by  Ström  and  Arctander.  The  first  of  these  followed  scarla- 
tina; there  is  no  autopsy  report.  According  to  Herve  three  similar  cases 
were  previously  reported  (1888)  by  Guelliot. 

Before  describing  my  own  case,  I  shall  briefly  mention  one  of  Henoch's: 
A  boy,  aged  five;  crisis  in  pneumonia  upon  the  22d  of  November.  Since  then 
complete  euphoria.  During  the  night  of  the  21th,  sudden  pains  in  the  left 
leg;  toward  morning  purpuric  areas  upon  the  chest  and  thighs,  an  hour  later 
upon  the  arms  and  lower  legs.  At  eleven  o'clock  in  the  morning  the  entire 
posterior  and  lateral  area  of  the  left  thigh  was  of  a  bluish  black  color ;  toward 
evening  also  the  left  calf  and  the  right  knee.  Temperature  101.8°  F.  In  no 
organ  could  anything  abnormal  be  detected.  During  the  night  of  the  21th 
the  entire  right  leg  with  the  exception  of  the  foot  became  bluish  black.  Great 
apathy  and  weakness;  urine  normal.  At  two  o'clock  in  the  morning  death 
in  collapse.     Autopsy  absolutely  negative. 

My  own  case  occurred  in  a  man,  aged  twenty-eight,  a  tinsmith,  who  upon 
the  23d  of  March,  1878,  was  admitted  to  Frerichs'  Clinic  in  a  comatose  con- 
dition, and  died  upon  March  25th.  No  history  could  be  obtained  from  the 
patient  nor  from  the  relatives.  Only  this  much  was  certain,  that  he  was  well 
and  able  to  work  two  days  previously.  The  disease  began  upon  the  morning 
of  the  21st.  At  that  time  the  patient  is  said  to  have  had  a  severe  chill  which 
forced  him  to  go  to  bed.  A  physician  who  was  called  the  next  morning  noted 
high  fever  and  ordered  his  removal  to  the  Charite.  The  diagnosis  of  typhus 
fever  was  made. 

March  23d,  nine  o'clock.  Patient,  a  very  muscular  man,  is  comatose,  con- 
stantly mumbling,  beating  the  air  with  tremulous  hands,  and  continually  throw- 
ing himself  about  in  bed.  The  face  appears  congested,  markedly  cyanotic, 
and  icy  cold.     The  middle  of  the  upper  lip  shows  a  protrusion  resembling  a 


MORBUS  MACULOSUS  WERLHOFII  483 

proboscis.  This  prominence  is  due  to  a  deep  hemorrhagic  suffusion  of  the 
mucous  membrane  beginning  at  the  border  of  the  lip,  almost  2  c.c.  in  breadth, 
and  reaching  posteriorly  almost  to  the  gums.  The  mucous  membrane  in 
this  area  appears  eroded  and  covered  with  thick  crusts,  upon  the  removal 
of  which  the  base  of  a  superficial  ulcer  of  bad  color  is  seen.  The  mucous 
membrane  around  the  border  of  the  ulcer  is  in  the  form  of  rolled-up 
shreds.  The  gums  are  bluish  red,  swollen,  in  part  hemorrhagicallv  infiltrated. 
The  lips  are  covered  with  sordes,  and  from  between  them  a  blood-stained 
mucus  exudes.  Under  the  conjunctivae  of  both  eyes  there  are  circular  flat- 
tened hemorrhages.  The  skin  is  smooth  and  dry.  The  color  is  chiefly 
yellowish,  but  is  modified  by  a  great  number  of  pale  to  dark  violet, 
irregularly  shaped  hemorrhages,  which  appear  partly  as  small  spots  and 
partly  as  flat  extravasations.  In  some  areas  these  flakes  disappear  on  pres- 
sure; at  most  points,  however,  they  persist.  Aside  from  these  spots  the 
skin,  on  account  of  stasis  and  uneven  filling  of  the  ve-.-els,  assumes  a  mar- 
bled appearance. 

Upon  the  lower  extremities  quite  large  suffusions  are  found  which  attain 
an  area  of  several  square  inches,  and  also  hemorrhages  which  almost  give  the 
impression  of  being  of  traumatic  origin.  Upon  the  external  surface  of  the 
thigh  they  are  quite  symmetric;  there  is  also  a  certain  symmetry  upon  the 
back.  In  the  joints  of  the  feet,  and  upon  the  dorsum  of  each  foot,  there  are 
extensive  suffusions,  reddish  blue  in  color,  almost  the  size  of  a  silver  dollar. 
Upon  the  right  lower  leg,  and  upon  the  dorsum  of  the  left  foot  there  are  also 
large  suffusions  besides  ulcers  covered  with  crusts.  The  sensorium  shows 
coma;  there  is  no  reaction  upon  deep  pricks  with  a  pin.  The  apex  of  the 
heart  cannot  be  felt;  cardiac  dulness  is  not  increased;  heart  sounds  clear. 
Lungs  Qormal.  Spleen  moderately  enlarged,  reaching  3  cm.  beyond  the  ante- 
rior axillary  line.  In  the  eye-ground  the  arteries  and  veins  are  dilated,  the 
papillary  limits  obliterated.  Xo  retinal  hemorrhages.  Temperature  reaches 
106.9°  F. 

Evening,  eight  o'clock.  Patient  is  comatose  with  closed  eyes,  moaning,  and 
assumes  the  dorsal  decubitus.  Respiration  increased  (32  per  minute)  and 
stertorous.  Patient  very  restless.  The  muscles  markedly  contracted.  There 
i-  anesthesia  of  both  cornea. 

Half-past  eleven  at  night.  Complete  unconsciousness.  Marked  prostra- 
tion. The  face  ig  covered  with  sweal  and  feel-  cool,  whereas  elsewhere  the 
skin  is  dry  and  burning  hot.  Temperature  107.6  1".  Upon  the  lefl  thigh, 
situated  externally,  a  single  bluish  red  suggillation  the  size  of  two  hands,  which 
has  resulted  from  the  confluence  of  a  Dumber  of  smaller  foci.     When  I  saw  the 

patient  three  hours  earlier-,  aboul  eighl  o'clock,  the  individual  point-  of  the 
eruption  were -till  separated  by  large  intervening  areas  of  healthy  skin.      Since 

eight  o'clock,  several  fresh,  bright  red  hemorrhages  have  appeared,  among 
them  one  the  size  of  a  silver  dollar.  Respiration  greatly  increased,  loud, 
snoring  in  character;  the  pulse  very  small  and  Boft,  L20  per  minute.  Paresis 
upon  the  righl  side  affecting  the  face  and  extremities.     Ptosis  of  the  right 

eyelid.     In   tl ye-ground   nothing  abnormal.     8edes  inscics.     Orine   acid, 

contain-  much  albumin  and  numerous  broad  casts. 


484  THE  HEMORRHAGIC  DIATHESES 

March  24th,  nine  o'clock  in  the  morning.  But  little  change  in  the  clin- 
ical picture.  Complete  insensibility.  Temperature  106.9°  F.  Upon  the  skin 
many  new  hemorrhages  have  appeared.  To  retain  the  picture  of  the  skin,  I 
asked  the  artist,  E.  Eyrich,  to  paint  a  water-color  of  the  case.  He  began  upon 
the  morning  of  the  24th  at  a  time  in  which  the  hemorrhages  were  so  close 
together  that  the  individual  flakes  upon  the  arms,  which  he  had  already  indi- 
cated in  contour,  assumed  an  entirely  different  size  and  configuration  from 
those  I  had  previously  seen.  While  he  was  working  on  his  picture  the  indi- 
vidual flakes  coalesced  and  enlarged.  As  this  condition  appeared  extremely 
strange  to  Mr.  Eyrich,  he  sent  for  me  in  order  that  I  might  note  the  coales- 
cence and  enlargement  of  the  individual  areas.  What,  however,  lent  a  pecul- 
iar character  to  these  hemorrhages  was  the  circumstance  that  the  larger  ones 
were  grouped  in  concentric  circles,  and  that  each  of  these  circles  showed  an 
entirely  different  color  tint.  This  peculiar  arrangement  was  caused  by  the 
striking  rapidity  with  which  the  individual  areas  developed  and  enlarged.  The 
older  center  appeared  much  darker  than  the  fresher  peripheral  hemorrhage; 
I  myself  observed  this  change  in  different  areas.  Thus,  areas  developed  in 
concentric  arrangement  which  consisted  of  three  to  four  rings  of  different  col- 
ors. The  development  of  these  hemorrhages  occurred  with  such  enormous 
rapidity  that  the  change  in  color  from  the  brightest  red  to  the  darkest  brown- 
ish red  could  be  noted  in  the  course  of  a  few  hours. 

Evening,  eight  o'clock.  Patient  in  collapse.  The  investigation  of  the  eye- 
grounds  shows  in  the  right  a  small  centrally  situated  retinal  hemorrhage,  and 
in  the  left  two  more. 

12.30  a.m.  Death.  The  temperature  taken  post  mortem  showed  a  rise 
to  108.8°  F. 

The  result  of  the  autopsy  was  very  unsatisfactory.  The  changes  worthy  of 
mention  were  the  following: 

Cloudy  swelling  of  the  liver,  spleen  and  kidneys.  White  stride  of  the 
medullary  substance  of  the  kidneys.  Very  slight  deposits  of  the  finest  ex- 
crescences upon  the  free  border  of  the  mitral  leaflet.  Multiple  hemorrhages 
in  all  serous  membranes. 

The  microscopic  investigation  of  the  skin  gave  an  entirely  negative  result; 
there  were  neither  vascular  emboli  nor  microorganisms  inside  the  vessels. 
Enormous  masses  of  streptococci  were  found  in  the  glomeruli  and  in  the  inter- 
tubular  capillaries  of  the  kidneys  as  well  as  in  the  deposits  upon  the  mitral 
valve. 

That  the  diagnosis  in  such  a  case  is  not  a  very  simple  one,  and  that 
great  diagnostic  errors  are  liable  to  occur,  is  taught  by  a  case  of  hemor- 
rhagic variola  in  which  the  clinical  symptoms  closely  resembled  those  of 
the  case  just  described,  and  only  late  in  the  course  of  the  disease  several  dis- 
tinct umbilicated  pustules  appeared  which  in  a  brief  time  broke  down,  leaving 
ugly  ulcers. 

The  diagnosis  of  hemorrhagic  smallpox,  if  the  latter  runs  its  course  without 
pustule  formation,  and  appears  during  a  period  in  which  other  cases  of  small- 
pox have  not  occurred,  may  give  rise  to  great  difficulties  on  account  of  the  sim- 
ilarity to  the  clinical  picture  of  purpura  fulminans.     In  the  course  of  severe 


MORBUS  MACULOSUS   WERLHOFII  485 

septic  diseases,  and  in  acute  leukemia  also,  extensive  cutaneous  hemorrhages 
occur. 

To  the  forms  of  the  hemorrhagic  diathesis  which  have  heen  described  we 
must  add  still  another  disease  which  lately  has  become  quite  prominent,  and 
which  by  some  authors  is  looked  upon  as  infantile  scurvy.  Yet  it  differs 
from  the  latter  affection  in  many  important  peculiarities.  The  disease  was 
described  in  185?  by  Möller  in  Königsberg  as  "acute  rachitis"  and  was  par- 
ticularly studied  by  Barlow  in  1883,  since  which  time  it  has  been  called  by  his 
name.  In  the  last  few  years  this  affection  has  been  repeatedly  the  subject  of 
close  investigation,  and  particularly  on  account  of  the  increasing  frequency  of 
the  disease  among  the  children  of  families  of  the  better  class,  has  become 
important.  It  occurs  exclusively  in  children  between  the  middle  of  the  first 
year  and  the  third  year  of  life.  The  onset  is  often,  but  not  always,  acute. 
After  a  few  days  of  general  ill  health,  occasionally  following  an  attack  of  diar- 
rhea, sensitiveness  and  difficulty  of  movement  in  one  or  both  lower  extremities 
appear,  with  sensitiveness  to  touch.  The  children  are  usually  found  with 
their  Limbs  extended  or  retracted  upon  the  abdomen,  immovable  in  bed.  Either 
active  or  passive  motion  is  painful.  Very  soon  a  spindle-shaped,  sensitive, 
smooth,  white  tumor  of  elastic  consistency  is  noted  in  the  course  of  the  diaph- 
ysis  of  one  or  both  thighs,  rarely  of  the  lower  leg  or  of  the  upper  extremities. 
Occasionally  crepitation  is  noted  in  the  epiphysial  border,  which  is  due  to  a 
loosening  of  the  latter. 

This  deeply  situated  subperiosteal  or  subperichondrial  tumor  in  the  tract 
of  the  long  tubular  bones  is  the  pathognomonic,  peculiar  sign  of  this  disease, 
compared  with  which  the  rachitic  or  scorbutic  symptoms  are  entirely  secondary. 
Neither  clinically,  by  puncture  or  incision,  nor  after  death,  has  pus  ever  been 
found  under  the  periosteum  of  the  diseased  bones,  but  invariably  pure  blood, 
and  there  is  no  case  on  record  in  which  it  has  ever  been  observed  that  the  cap- 
sule of  tin'  joint,  in  spite  of  its  close  proximity,  was  implicated  in  the  process. 

To  these  previously  mentioned  symptoms  frequently,  but  by  no  means 
always,  the  symptoms  of  the  hemorrhagic  diathesis,  of  scurvy  and  of  rickets, 
are  added.  T<>  the  latter  has  been  attributed  tin'  great  tendency  to  sweating, 
particularly  of  the  occiput,  as  well  as  the  swelling  of  the  epiphyses.     Scurvy 

is    thought    to   explain    the    loosening  and    spongy    swelling   of    the  gums    with 

fetor,  and  the  tendency  to  hemorrhage,  especially  in  the  cases  where  teeth 
are  already  present.  Fever  and  gastric  symptoms  are  frequent.  Occa- 
sionally purpura,  hemorrhages  into  the  mucous  membranes,  and  albuminuria 
occur;  Benoch  mentions  hemorrhages  ander  the  periosteum  of  the  frontal 
bone,  into  the  eyelid-,  and    into  the  retrobulbar  tissue  with  exophthalmos. 

The  appearance  of  the  children  is  anemic,  but  very  rarely,  either  by  hemor- 
rhage or  other  complications,  doe-  death  occur. 

Regarding  the  etiology  of  this  important  and  interesting  disease,  it  has 
been  maintained  more  ami  more  lately  that  improper  nourishment  i-  respon- 
sible. While  by  some  authors  the  too  great  uniformity  of  the  nutrition  has 
been  Looked  upon  a-  the  cause,  others  emphasize  the  absence  of  fresh  food.  In 
the  exhaustive  American  collective  investigation  (Boston  Med.  and  Surg.  Jour- 
nal, 1898),  and   in  a  greal   number  of  individual  observations,  it   ha-  been 


486  THE  HEMORRHAGIC  DIATHESES 

shown  that  Pasteurized  and  sterilized  milk  if  used  exclusively  may  cause  Bar- 
low's disease,  and  that  sterilization  in  the  Soxhlet  apparatus  is  sufficient  to 
produce  it.  Lately  it  has  been  assumed  that  the  duration  of  the  heating  proc- 
ess of  the  milk  is  the  most  important  factor,  but  Heubner  believes  that  heating 
from  ten  to  fifteen  minutes  is  not  productive  of  harm. 

H.  Neumann  1  states  in  regard  to  this  matter :  "  From  my  own  experience 
of  the  conditions  in  Berlin  for  the  last  five  years,  the  following  may  be  main- 
tained: In  nutrition  with  artificial  milk  preparations  Barlow's  disease  occurs 
very  rarely,  either  from  the  fact  that  the  prolonged  use  of  these  foods  has 
become  rarer,  or  that  more  care  is  taken  in  sterilization.  In  the  year  1899  I 
saw  but  one  case  which  was  due  to  Gartner's  '  fat-milk.'  Considering  the 
mode  of  preparation  of  this  food  only  the  sterilization,  not  the  chemical  treat- 
ment, could  play  a  role ;  in  my  case  the  milk  was  sent  for  weeks  in  the  sum- 
mer to  the  seashore,  and  for  this  purpose  was  previously  heated  to  a  very  high 
degree.  In  another  case,  in  the  year  1899,  cow's  milk  prepared  in  a  labora- 
tory was  powerfully  heated — up  to  the  point  of  browning.  Up  to  the  year 
1900,  I  had  seen  four  children  who  were  taken  ill  in  spite  of  the  fact  that  the 
thoroughly  reliable  raw  milk  was  in  two  cases  heated  only  for  fifteen  minutes, 
and  in  two  cases  for  only  ten  minutes  in  the  Soxhlet  sterilizer.  In  two  of 
these  cases  infant  food  was  added  to  the  milk,  but  I  do  not  desire  to  attach 
any  importance  to  this.  I  should  like  to  mention  here,  however,  that  in  two 
of  these  cases  intestinal  catarrh  preceded  the  disease;  in  the  third  case  dys- 
pepsia was  present  which  may  have  hastened  the  appearance  of  Barlow's  dis- 
ease. On  the  other  hand  a  case  occurred  in  the  entirely  normal  child  of  a 
colleague,  and  in  this  case  the  preparation  of  the  milk  must  be  held  entirely 
responsible  for  the  disease  (fifteen  minutes  in  the  Soxhlet  apparatus).  Since 
the  year  1901  Barlow's  disease,  at  least  according  to  my  experience  (which  is 
also  confirmed  by  Heubner)  has  increased  in  frequency  in  Berlin,  and  this 
makes  it  possible  minutely  to  investigate  a  very  remarkable  fact :  For  tbe 
fourteen  children  that  I  had  an  opportunity  of  seeing  in  this  time  the  Soxhlet 
apparatus  was  always  used,  and  in  seven  cases  the  milk  was  sterilized  for  ten 
minutes,  in  two  cases  for  fifteen  minutes,  and  in  five  it  was  boiled  for  a  longer 
period  than  this.  In  spite  of  the  fact  that  among  our  well-to-do  classes 
infant's  milk  may  be  obtained  from  a  number  of  reliable  dairies,  the  milk 
for  the  fourteen  children  treated  by  me  was  all  obtained  from  the  same  dairy, 
and  from  a  dairy  which  since  that  time  has  employed  its  entire  product  in  a 
laboratory  for  heating,  from  which  no  exact  records  can  be  obtained.  While, 
according  to  my  experience,  the  mere  boiling  of  this  milk  does  no  harm,  the 
combination  of  sterilization  according  to  Soxhlet  with  previous  Pasteurization 
may  produce  Barlow's  disease. 

"Besides  the  cases  cited  above,  I  later  saw  seven  others,  the  infants  being 
from  six  to  ten  months  of  age  when  they  came  under  treatment.  Six  of  these 
patients  had  been  fed  from  birth  on  B's  milk;  it  was  boiled  for  ten  or  fifteen 
minutes  in  the  Soxhlet  apparatus,  or  ten  to  twenty  minutes  in  Hartmann's 
milk  boiler;  in  one  child  only  did  the  disease  develop  while  exclusively  nour- 

i  "  Verh,  des  Vereines  für  innere  Medicin  in  Berlin,"  1903. 


MORBUS  MACULOSUS  WERLHOFII  487 

ished  by  condensed  Swiss  milk ;  but  "with  the  use  of  B's  milk  it  developed  to  a 
great  extent.  Therefore,  to  summarize,  Xeumann  has  observed  in  the  last 
eighteen  months  twenty-one  cases  of  Barlow's  disease,  of  which  twenty  may 
be  referred  to  the  use  of  the  same  millc.  If  these  cases  were  left  out  of  con- 
sideration Barlow's  disease  would  be  as  rare  as  formerly.  Therefore,  its  in- 
creased incidence  may  be  referred  to  a  purely  accidental  and  perfectly  recog- 
nizable cause." 

PATHOLOGICAL   ANATOMY 

Cases  of  simple  purpura  which  terminate  fatally  are  rare.  If  death  occurs, 
this  is  either  the  result  of  profound  anemia  after  profuse  hemorrhage  or  in 
consequence  of  complications  or  sequels.  For  this  reason  autopsy  findings  are 
very  scanty.  The  cadavers  are  extremely  pallid,  also  somewhat  bloated,  and 
usually  covered  with  hemorrhagic  blotches,  which  have  taken  on  the  livid  post 
mortem  discoloration  of  altered  hemoglobin.  The  muscles  and  fatty  tissue  are 
in  most  of  the  cases  unchanged ;  only  in  very  protracted  cases  is  the  latter 
decreased.  According  to  the  intensity  of  the  disease  we  find  more  or  less 
extensive  hemorrhages  upon  the  mucous  and  serous  membranes,  and  under  cer- 
tain circumstances  these  cover  large  areas.  Occasionally  these  hemorrhages 
are  distributed  to  an  astonishing  degree  upon  the  mucous  membrane  of  the 
bronchi,  of  the  digestive  canal,  in  the  renal  pelvis,  ureter,  bladder,  etc.  At 
times  the  mucous  membrane,  if  we  strip  off  the  inspissated  blood  crusts,  may 
show  superficial  erosions.  Freshly  effused  blood  is  also  occasionally  found 
in  the  mucous  membranes  of  the  bronchi  with  bloody  mucus.  This  is  also 
noted  in  the  renal  pelvis  and  in  the  intestinal  canal.  In  the  cavities  of  the 
serous  membranes,  in  the  pericardium,  in  the  pleura,  and  in  the  peritoneum. 
as  well  as  in  the  cavities  of  the  joints,  besides  small  ecchymoses,  we  occasionally 
find  larger  effusions  of  a  purely  hemorrhagic  character,  so  that  we  are  deal- 
ing with  hemopericardium,  hemothorax,  hemarthrosis,  etc.  We  also  find  par- 
enchymatous hemorrhages,  particularly  in  the  liver  and  kidneys;  in  isolated 
cases  the  adrenals  have  been  found  containing  bloody  infarcts.  Tn  the  mu- 
seum collection  at  my  hospital  I  have  two  such  hemorrhagic  adrenal  infarcts, 
each  about  the  size  of  a  medium-large  apple.  The  spleen  in  a  certain  number 
of  cases,  but  by  no  means  invariably,  has  been  found  enlarged;  in  isolated 
instances  it  contains  the  same  wedge-shaped  hemorrhagic  infarct-.  In  the 
protracted  cases  running  a  febrile  course  there  is  cloudy  -welling  of  the  Large 
parenchymatous  gland-  besides  swelling  of  IVyer's  patches  and  of  the  mesen- 
teric glands.  The  Bame  is  observed  in  the  bone-marrow,  upon  the  endocardium, 
the  vascular  intima  and  the  neurilemma.  The  bone-marrow  has  been  found 
traversed  by  profuse  and  small  hemorrhages.  Pigment  infiltration,  due  to 
the  decomposition  of  eztravasated  blood,  has  also  been  observed  in  different 
organs,  particularly  in  the  lymph-glands.  The  pigment  appears  in  flaky 
masses  and  consists  entirely  of  hydrated  <>\id  of  iron. 

Nothing  is  known  of  other  constant   change-:   minute  reports  are  lacking 

in  regard  to  the  condition  of  the  membranes  of  the  joints  and  cavities,  particu- 
larly in  those  cases  in  which  during  life  rheumatic  pains  weiv  present.     The 

knee-  and    foot-joint-  are   the  one-  which   are  chiefly  attacked   with  arthritic 


488  THE  HEMORRHAGIC  DIATHESES 

symptoms  in  purpura;  for  the  present  we  must  content  ourselves  with  this 
fact,  and  await  further  knowledge  and  results  from  the  autopsy  findings  of 
the  milder  forms  of  the  hemorrhagic  diseases.  In  a  case  of  peliosis  rheumatica 
from  Traube's  Clinic,  upon  which  an  autopsy  was  held,  the  findings  in  the 
joints  did  not  differ  from  those  of  acute  articular  rheumatism  and  gonorrheal 
rheumatism  (see  above).  The  autopsy  report  is  as  follows:  The  right  knee 
appears  somewhat  thicker  than  the  left.  In  the  external  parts  there  is  little 
that  is  abnormal ;  but  in  the  interior  of  the  joint  is  a  very  marked,  fine,  dark 
red  injection  of  the  ligamenta  cruciata,  as  well  as  of  the  entire  capsule  of  the 
joint,  besides  a  gelatinous  swelling  of  the  same,  especially  marked  about  the 
patella.  The  cartilage  of  the  joints  and  the  semilunar  cartilage  show  no 
abnormality.  The  fluid  of  the  joint  is  scant,  somewhat  viscid,  and  darker  than 
normal. 

In  the  main  no  constant  changes  have  been  found,  not  even  such  as  might 
be  referred  to  anemia.  The  valvular  apparatus  of  the  heart  is  invariably 
intact ;  in  one  case  of  fulminant  purpura  described  by  me  there  was  a  slight 
deposit  of  fine  warty  excrescences  upon  the  free  border  of  the  mitral  leaflet, 
as  occurs  so  frequently  in  any  disease  running  an  acute  course.  But  even  these 
have  in  other  cases  been  entirely  absent. 

I  shall  revert  later  to  the  changes  in  the  blood,  that  is,  in  its  composi- 
tion ;  here  I  will  only  briefly  mention  that  some  authors  have  found  the  coagu- 
lability of  the  blood  to  be  diminished,  a  finding  which  still  requires  con- 
firmation. 

The  spleen  and  lymph-glands  show  no  constant  alterations,  but  the  former 
organ  has  repeatedly  been  found  enlarged,  and  pappy  softening  of  the  pulp 
has  been  noted  (Billroth).  It  remains  a  question  whether  this  is  not  due  to 
post  mortem  change. 

The  kidneys  occasionally  reveal  a  condition  of  hemorrhagic  inflammation. 
In  cases  of  chronic  albuminuria  I  several  times  observed  isolated  small-celled 
foci  of  infiltration  in  the  cortex.  In  other  cases  in  which  albuminuria  had 
existed  for  many  months  these  were  absent. 

Hemorrhages  upon  the  retina,  as  well  as  upon  the  cornea,  have  been  deter- 
mined during  life  and  confirmed  post  mortem.  Upon  microscopic  investiga- 
tion of  the  eyes  in  question  I  found  the  vessels  intact  in  both  membranes  of 
the  eye,  which  is  by  no  means  the  case  in  analogous  hemorrhages  in  the  eyes 
of  patients  with  renal  disease.  More  frequently  meningeal  and  cerebral  hem- 
orrhages have  been  found  at  the  autopsy,  but  these  have  been  looked  upon  as 
the  cause  of  the  epileptiform  attacks  and  paralyses  which  had  occurred  dur- 
ing life. 

The  changes  in  the  vessels  in  the  course  and  in  the  vicinity  of  ecchymoses 
have  been  described  explicitly  in  the  etiology,  and  the  investigations  of 
v.  Kogerer,  Rieh]  and  Leloir  have  been  mentioned.  Hayem  states  that  throm- 
boses have  formed  in  the  finer  arteries  by  the  agglutination  of  leukocytes. 
Other  authors  found  amyloid  degeneration  of  the  capillaries  in  the  vicinity 
of  the  petechias  (?).  Stroganow,  whose  investigations  I  have  already  re- 
ferred to,  discovered  in  the  aorta,  in  the  vena  cava,  and  in  the  veins  of  the 
liver  infiltrations  of  the  intima  with  red  blood-corpuscles  which  from   the 


MORBUS  MACULOSUS  WERLHOFII  489 

lumen  of  the  vessels  appeared  to  have  directly  penetrated  the  intima  per  dia- 
pedesin.  But  this  Latter  observation  explained  the  nature  of  the  disease  and 
the  occurrence  of  the  hemorrhages  as  little  as  any  of  the  previously  mentioned 
researches. 

Among  the  complicating  processes  which  occasionally  result  in  death  I 
shall  enumerate  the  following:  Large  effusions  into  the  pleura  and  abdomen, 
pulmonary  infarcts,  purulent  peritonitis,  croupous-diphtheritic  processes  of 
the  small  intestine,  pneumonia,  necrosis  of  the  intestine,  perforative  perito- 
nitis, gangrene  of  the  large  intestine  with  swelling  of  the  mesenteric  glands, 
ecchymoses  and  ulcers  of  the  descending  colon. 

Regarding  the  bacteriologic  findings,  besides  those  described  in  the  etiol- 
ogy. 1  should  like  to  discuss  here  some  further  points.  Tizzoni  and  Giovannini 
isolated  from  a  case  of  purpura  hemorrhagica  in  which  secondary  impetigo 
contagiosa  developed,  and  upon  which  autopsy  was  held,  a  bacillus,  the  bacillus 
hemorrhagicus  velenosus.  In  the  pustules  of  impetigo  surrounded  by  the 
purpuric  areas  of  the  skin  this  bacillus  was  found  with  the  staphylococcus 
pyogenes  aureus;  it  was  also  found  in  the  liver  and  in  the  venous  blood,  but 
not  in  the  spleen  nor  in  the  kidneys.  The  staphylococcus  was  present  in  the 
pure  hemorrhagic  foci  of  the  skin,  as  well  as  in  the  kidneys.  The  bacillus 
hemorrhagicus  velenosus  is  inimotile,  0.2-0.4  fi  broad,  0.7-1.3/*  long;  it  stains 
well  with  anilin  colors,  but  not  according  to  Gram.  Spore  formation  was  not 
observed;  bul  there  was  a  certain  resistance  to  «Irving.  The  colonies  showed 
irregular  contours  which  resembled  coiled  locks  of  hair,  and  did  not  become 
fluid.  In  a  stab  culture  they  showed  granular  growth,  and  upon  agar  a 
growth  similar  to  that  upon  gelatin.  In  older  cultures  a  pungent  odor  is 
noticeable.  Upon  potato  only  a  superficial  growth  of  an  indistinct  nature 
with  a  dark  yellowish  discoloration  at  the  point  of  inoculation  is  observed, 
upon  culture  in  bouillon  moderate  turbidity  appears,  later  becoming  mucoid. 
The  bacillus  LS  pathogenic  in  rabbits,  dogs,  and  guinea-pig-,  but  not  in  pigeons 
and  mice.  The  bacilli  increase  only  locally  with  formation  of  edema.  They, 
however,  give  rise  to  fever,  hemorrhagic  nephritis,  vomiting,  hemorrhagic 
diarrhea,  cutaneous  hemorrhages.  Upon  autopsy  of  the  infected  animals 
there  are  found  incoagulability  of  the  blood,  coagulation  necrosis  of  the  liver 
and  renal  epithelium,  with  a  normal  condition  of  the  spleen.  Cultures  steril- 
ized at  70°  C.  produce  albuminuria.  Repeated  injection-  of  Buch  cultures 
confer  immunity  to  subsequent  infection. 

Kolb.1  of  the  Imperial  Bureau  of  Health,  investigated  bacteriologically 
five  cases  of  true  idiopathic  purpura:  Among  these  were  thr »ses  of  pur- 
pura fulminans  which  terminated  fatally  after  a  brief  course;  the  other  two 
cases  recovered.     Microscopic  investigation,  cultures  and   inoculation  of  the 

blood  taken  from  the  living  patient  into  mice,  guinea-pigs,  rabbit-  and  pigeons, 

gave  do  results.  Positive  results  were,  however,  obtained  by  the  bacteriologic 
investigation  of  the  cadaver-.  There  were  examined:  (a)  Blood  from  the 
heart  and  from  the  portal  vein:  (l>)  some  area-  of  the  -kin  containing  char- 
acteristic purpura;  (<)  particles  of  hemorrhagic  portion-  from  the  lung:  (d) 


i  Arbeiten  aus  dem  kaiserlichen  Oesundheitsamte,  Bd.  \ü.  1891. 


490  THE  HEMORRHAGIC  DIATHESES 

the  liver,  spleen  and  kidneys;  (e)  hemorrhagic  portions  of  the  intestine;  (f) 
lymph-glands  from  the  thoracic  and  abdominal  cavities. 

In  the  sections  from  the  large  hardened  glands  of  the  abdomen,  as  well  as 
in  the  hemorrhagic  cutaneous  areas,  there  was  found,  after  staining  with 
methylene-blue  and  after  the  Gram-Weigert  process,  a  moderately  large 
bacillus  averaging  from  1-2  /x  in  length  and  0.8  fx  in  breadth  with  rounded 
ends.  The  bacilli  were  especially  pro-fuse  in  the  spleen,  some  in  the  small 
blood-  and  lymph-vessels  forming  larger  clumps,  some  also  in  the  interstitial 
tissue,  though  here  not  so  numerous  as  in  the  vessels,  but  found  lying  sepa- 
rated from  one  another;  now  and  then  longer  threads  were  found  due  to  a 
juxtaposition  of  the  individual  bacilli  end  to  end.  For  the  most  part  two  rods 
were  found  placed  together  lengthwise  (diplobacilli).  In  the  kidneys  the  bacilli 
were  mostly  met  with  in  the  glomeruli,  but  were  here  not  so  numerous  as  in 
the  spleen.  It  was  also  possible  to  find  the  bacillus  in  sections  from  the  liver, 
and  in  sections  of  cutaneous  hemorrhagic  areas  in  which,  even  in  the  lowest 
cellular  layer  of  the  corium,  scattered  bacilli  were  found.  Particularly  in- 
structive pictures  were  furnished  by  sections  of  hemorrhagic  glands.  In  fresh 
sections  from  organs  the  same  variety  of  bacteria  was  demonstrated.  The 
bacillus  hemorrhagicus  Kolb  flourishes  upon  gelatin.  The  matured  colonies 
are  circular  in  form,  with  many  constrictions  and  serrations;  in  the  interior 
fine  furrows  are  seen,  and  toward  the  border  a  more  granular  appearance 
becomes  prominent.  In  stab  culture  after  a  few  days  colonies  are  found 
partly  isolated,  partly  coalescent,  with  superficial  flat,  hyaline  extensions 
along  their  serrated  borders.  Upon  inoculation  a  thin  leaf-like  distribution 
of  a  whitish  blue  color  and  of  porcelain-like  transparency  with  indentations 
and  serrated  borders  is  observed  along  the  entire  course.  Kolb's  bacillus  grows 
upon  agar,  as  in  the  gelatin  stab  culture,  and  somewhat  more  slowly  upon  blood 
serum.  Upon  potato  a  white,  moist,  glistening  streak  is  noted  along  the 
course  of  inoculation.  In  bouillon  cultures  a  feebly  alkaline  medium  is  the 
best.  Even  on  the  first  day  the  solution  shows  a  general  cloudy  turbidity.  As 
the  growth  advances  the  bacteria  sink  to  the  bottom.  In  pure  culture  the 
bacillus  appears  as  a  short,  oval,  somewhat  plump  rod  with  rounded  ends; 
usually  two  are  found  together.  Its  length  amounts  to  0.8-1.5  /x.  The  appar- 
ent threads  which  are  frequently  observed  may  attain  in  pure  culture  a  length 
of  30  p.    The  bacillus  has  no  motility,  and  is  a  facultative  aerobe. 

Kolb's  bacillus  is  pathogenic  in  mice,  and  rabbits  and  pigeons  are  suscep- 
tible; on  the  other  hand,  guinea-pigs  very  rarely  or  never  succumb  to  the 
infection.  In  susceptible  animals  the  clinical  picture  corresponds  to  human 
purpura  hemorrhagica.  In  rabbits  the  characteristic  purpuric  spots  may  be 
produced  with  cultures  free  from  bacteria  and  mice  may  be  killed  in  this  way. 

SPECIAL  SYMPTOMATOLOGY 

The  most  characteristic  and  prominent  symptom  of  the  disease,  forming 
its  distinguishing  feature,  and  attracting  most  attention,  is  the  purpura  which 
develops  upon  an  entirely  normal  skin  without  producing  any  inflammatory 
disturbance.  As  the  areas  of  the  skin  upon  which  the  hemorrhages  appear 
are  up  to  the  moment  of  their  development  entirely  intact,  we  may  assert  with 


MORBUS  MACULOSUS  WERLHOFII  491 

great  probability  that  these  hemorrhages  have  their  origin  chiefly  in  internal 
causes,  and  are  the  expression  of  the  so-called  hemorrhagic  diathesis.  Al- 
though the  intensity  and  extent  of  the  hemorrhagic  efflorescence  is  no  exact 
indication  of  the  severity  of  the  disease,  observation  nevertheless  proves  that 
the  small,  isolated,  and  rapidly  disappearing  petechia?  represent  the  milder 
type,  while  the  more  distributed  and  very  diffuse  suggillations,  with  a  pro- 
tracted course  and  a  tendency  to  repeated  relapses,  indicate  a  more  severe 
form  of  the  disease.  At  the  same  time,  all  the  transitional  stages  from  the 
mildest  to  the  severest  of  cutaneous  affections  may  occur,  and  cause  the  body 
to  appear  as  if  spattered  with  a  large  brush  dipped  in  blood.  There  may  be 
extravasations  of  the  size  of  a  plate,  which  occasionally  leave  but  few  large 
areas  unaffected,  and  are  of  a  violet  to  a  dark  red  color.  Deep-seated  flat 
hematomata  may  also  arise  and  extend  into  the  muscles,  and  over  these  the 
skin  presents  the  well-known  changes  of  extravasated  hemoglobin,  showing  all 
the  colors  of  the  rainbow.  Finally,  streaks  and  strias-like  "  vibices  "  appear, 
particularly  in  the  flexure  of  the  knees,  which  resemble  analogous  conditions  _ 
in  scurvy,  and  which  go  through  all  the  changes  in  tint  and  shade  from  dark 
blue  to  greenish  yellow. 

We  have  still  to  consider  the  relation  of  the  hemorrhagic  efflorescences  to  the 
complications,  particularly  to  the  arthritic  affections  and  to  the  gastric  phe- 
nomena. 

The  appearance  of  the  purpuric  areas  in  the  complicated  cases  differs  in  no 
respect  from  ordinary  purpura.  Occasionally  the  eruption  begins  with  the 
appearance  of  typical  urticaria  with  vesicles,  which  gradually  become  filled 
with  a  hemorrhagic  fluid,  and  soon  dry  in  the  way  so  well  known  in  urticaria; 
the  pustules  then  collapse  and  disappear  without  leaving  residua.  In  other 
cases  the  urticarial  vesicle  leaves  behind  it  a  hemorrhagic  area.  Occasionally 
in  the  same  individual  alternating  attacks  of  urticaria  and  purpura  are  noted. 
It  has  often  been  remarked  that  patients  who  suffer  from  conditions  of  this 
kind  have  previously  suffered  from  urticaria.  Sometimes  the  development  of 
petechia?  is  preceded  by  the  formation  of  diffuse  erythema,  in  the  course  of 
which  occasional  miliaria]  vesicles  appear. 

The  changes  which  hemoglobin  undergoes  in  the  hemorrhagic  eruptions 
of  the  skin  correspond  as  a  rule  to  the  well-known  processes.  Occasionally, 
however,  we  see  very  extensive  suggillations  of  enormous  size  and  of  very 
different  ages;  in  such  cases  extraordinarily  striking  pictures  are  noted  which 
confuse  the  inexperienced,  particularly  so  if  recent  hemorrhages  are  super- 
added to  old  ones,  which  represent  all  the  color  modifications  and  all  the  tints 
of  altered  blood.  After  absorption  pigment  is  noted  with  the  naked  eye  only 
in  those  cases  in  which  huge  extravasations  of  blood  have  occurred.  Even 
this,  however,  disappears  after  some  time,  so  thai  with  the  lapse  of  week-  or 

month-  nothing  remains  to  indicate  the  process  which   has  taken    place.      The 

conditions  are  differenl  in  the  microscopic  investigation;  the  pigment  depos- 
ited and  accumulated  in  the  rete  Malpighii  remains  there  for  a  long  time, 
bo  thai  after  some  months  after  the  disease  has  run  its  course  we  are  still 
able  to  recognize  in  this  area  that  the  Bkin  was  once  the  Beai  of  a  decided  effu- 
sion  of  blood. 


492  THE  HEMORRHAGIC  DIATHESES 

Besides  small  hemorrhages,  not  infrequently  other  forms  of  deeply  situated 
hemorrhages  take  place  in  the  subcutaneous  tissues;  indurated,  reddish  or 
bluish,  scarcely  movable  suggillations  and  infiltrations  appear  between  the 
periosteum  and  the  external  skin  (for  example,  upon  the  tibia  and  the  vault, 
of  the  skull),  also  in  areas  in  which  no  bones  lie  just  beneath  the  so-called 
erythema  nodosum.  These  larger  and  smaller  infiltrations,  over  which  the 
skin  shows  a  bluish  discoloration  and  is  but  slightly  movable,  are  found  par- 
ticularly in  areas  upon  which  external  pressure  has  been  exerted  for  some 
time.  These  are  found  occasionally  in  the  course  of  purpura  with  and  with- 
out arthritic  affection,  but  they  do  not  make  the  slightest  impression  upon  the 
course  of  the  disease. 

Regarding  the  seat  of  the  petechia,  the  lower  leg  is  most  frequently 
attacked;  next,  the  abdomen,  the  back  and  the  upper  extremities;  most  rarely, 
the  face  and  the  mucous  membrane  of  the  mouth. 

I  must  not  omit  to  mention  that  in  undoubted  simple  purpura  the  gums 
are  sometimes  very  decidedly  affected,  while,  as  is  well  known,  cases  of  scurvy 
occur  without  disease  of  the  gums.  But  we  should  judge  very  superficially  if 
we  drew  from  this  the  conclusion  that  the  latter  is  a  mild  form  of  scurvy,  or 
the  former  a  severe  purpura.  In  this  connection  I  will  refer  to  the  descrip- 
tion of  scurvy  (see  p'age  402),  and  will  here  simply  state  the  fact  that  in 
the  course  of  purpura  disease  of  the  gums  occasionally  occurs,  and  may  lead 
to  severe  changes  therein  with  fetor  but  without  the  sponginess  and  ulceration 
and  destruction  of  the  gums  or  the  loosening  of  the  teeth  which  is  so  common 
in  the  case  of  scurvy. 

The  number  of  successive  hemorrhagic  eruptions  on  the  skin  varies  within 
wide  limits  from  one  to  twenty  attacks;  on  an  average,  four  attacks  have  been 
mentioned. 

The  relation  between  the  time  of  the  appearance  of  cutaneous  hemorrhages 
to  the  other  symptoms  is  a  very  changeable  one;  usually,  it  is  true,  the  former 
is  the  earlier  symptom.  But  in  children,  according  to  the  descriptions  of 
v.  Dusch,  this  rule  does  not  hold  and  very  frequently  attacks  of  severe  intes- 
tinal phenomena  without  the  simultaneous  appearance  of  purpura  are  ob- 
served, or  vice  versa.  An  inflammatory  effusion  is  present  in  one  or  more 
joints  which,  on  account  of  its  long  existence,  may  remain  until  several  crops 
of  purpura  have  appeared  and  disappeared.  An  effusion  of  this  type  in  one 
or  another  joint  is  somewhat  more  rare  in  children  than  in  adults,  in  whom  it 
appears  in  about  50  per  cent,  of  the  cases ;  edema  in  the  surroundings  of  the 
affected  joint  is  met  with  particularly  in  adults. 

The  effusion  is  rarely  very  marked,  never  becomes  purulent,  and  leaves  no 
disturbances  of  motion  behind.  The  visible  swellings  are  preceded  in  almost 
all  cases  by  arthritic  pains  or  by  sensitiveness  upon  pressure  and  movement. 
The  joints  of  the  lower  extremities  are  most  often  attacked,  after  this  the 
joints  of  the  hands.  The  differential  diagnosis  between  purpura  rbeumatica 
and  purpura  gonorrhoica  may  be  very  difficult  under  some  circumstances,  espe- 
cially if  the  patient  denies  a  preceding  gonorrhea.  The  prognosis  of  the  former 
is  usually  favorable.  Poliosis  rheumatica  differs  from  acute  articular  rheu- 
matism in  its  entire  clinical  picture,  in  the  course  of  its  fever,  particularly  in 


MORBUS  MACULOSUS  WERLHOFII  493 

the  absence  of  a  tendency  to  profuse  sweats  and  endocardial  or  pericardial 
implication,  and.  finally,  by  the  fact  that  very  frequently  the  joint  phe- 
nomena are  quite  transitory  and  appear  much  milder  than  in  the  other  affec- 
tion, although  this  cannot  be  designated  as  a  constant,  invariable  rule. 

The  relation  of  the  arthritic  affection  to  the  hemorrhagic  disease  appears, 
apart  from  the  arthritic  hemorrhages,  to  be  by  no  means  clear.  It  becomes 
somewhat  less  obscure  if  we  consider  that  in  the  hemorrhagic  diathesis  the 
serous  membranes  are  especially  liable  to  attack  and  we  know  from  the  analogy 
of  other  arthritic  affections  that  the  serous  membranes  bear  a  certain  relation 
to  the  joints,  so  that  both  are  often  attacked  at  once. 

It  is  hard  to  decide  whether  the  implication  of  the  joints  of  the  knee  and 
of  the  foot,  so  frequently  observed,  can  be  explained  by  ibe  suggestion  that 
the  general  predisposition  to  purpura  would  naturally  fall  heaviest  on  those 
joints  whose  function  it  is  to  carry  the  weight  of  the  body,  and  which  for 
tin-  reason  are  particularly  exposed.  Of  course  this  explanation  should  be 
similarly  operative  in  other  multiple  joint  affections. 

I  suppose  that  the  sum  of  our  positive  knowledge  is  this:  There  is  an  ana- 
tomic relationship  between  the  joint  cavities  with  the  serous  membranes;  hem- 
orrhages into  these  occur  under  the  influence  of  the  hemorrhagic  diathesis.  Yet, 
as  regards  the  arthritic  affections  in  purpura  hemorrhagica  and  in  morbus 
maculosus  Werlhofii,  it  appears  to  me  by  no  means  so  firmly  established  as  in 
the  analogous  joint  disease  in  scurvy  and  hemophilia  thai  these  are  invariably 
and  ah.-olutely  hemorrhagic.  The  clinical  symptoms,  results  of  occasional 
joint-puncture  and  the  autopsy  findings  in  the  Traube-Leuthold  case  (already 
mentioned  three  times)  are  all  opposed  to  this. 

Of  the  intestinal  symptoms  in  severe  and  complicated  forms  of  the  disease 
painful  colics  are  the  most  characteristic.  These  resemble  the  form  seen  in 
chronic  lead-poisoning.  The  seat  of  pain  is  referred  to  the  region  of  the  navel, 
from  which  it  radiates  to  various  places.  Although  at  the  autopsy  hemorrhagic 
infiltrations  of  the  intestine  with  ulcer  formation  in  various  areas  have 
repeatedly  been  found,  v.  Dusch  advises  caution  in  the  interpretation  of 
reports  from  the  patient:  "Bloody  vomiting  occurred.*'  or,  "Tarry  hemor- 
rhagic discharges  occurred.'"  He  is  of  the  opinion  that  such  reports  prove 
nothing,  and  especially  not  that  the  -cat  of  hemorrhage  is  actually  within  the 
intestinal  canal.  It  must  he  remembered  that  in  small  children,  in  sleep, 
ami  in  comatose  patients  who  maintain  the  dorsal  decubitus  considerable 
quantities  of  blood  may  How  unnoticed  from  the  nose  int<>  the  Btomach  and 
be  discharged  by  rectum.  I  cannot  suppress  the  opinion  that  this  explanation 
M'cin-  very  forced  and  artificial,  and  I  do  not  doubl  that  in  the  cases  of  Bevere 
colic  actual  enterorrhagia  often  occur-,  a  view  which  is  more  firmly  founded 
upon  the  fact  that  the  colics  decrease  decidedly  in  severity  after  profuse  hem- 
orrhage from  the  intestine. 

Albuminuria  i-  by  no  mean-  a  rare  complication  in  the  coiir-e  of  the  vari- 
ous form-  of  the  hemorrhagic  diathesis,  for  the  mo-t  part  without  an  inflam- 
matory condition  of  the  kidneys.  In  some  cases  I  have  -ecu  the  excretion  of 
albumin  in  every  attack,  ami  occasionally  it  extends  into  the  intervals.  In 
other  cases  the  excretion  of  albumin  Lasts  for  ten  month.-  ami  longer,  hut 


494  THE  HEMORRHAGIC  DIATHESES 

finally  disappears  spontaneously  without  any  medication.  In  other  (but 
much  rarer)  cases  of  morbus  maculosus  Werlhofii,  contracted  kidney  develops, 
becomes  chronic  and  gradually  leads  to  death.  According  to  my  observations 
of  many  cases,  even  after  a  simple  albuminuria  (i.  e.,  without  casts  and  leuko- 
cytes) has  existed  for  many  months,  the  hope  of  recovery  must  not  be  given  up, 
for  this  condition  may  disappear  as  suddenly  as  it  arose. 

In  regard  to  the  changes  in  the  eye,  retinal  hemorrhages  have  occasionally 
been  observed;  they  sometimes  show  white  centers.  Hemorrhages  have  also 
been  noted  in  the  choroid  and  in  the  sclera.  The  flow  of  tears  may  also  show  a 
reddish  discoloration.     Nettleship  saw  bilateral  neuritis  after  purpura. 

We  have  no  definite  knowledge  of  the  causes  of  febrile  phenomena  which 
either  precede  the  cutaneous  hemorrhages  or  occur  in  the  course  of  the  same, 
and  which  also  are  not  rarely  absent.  A  more  exact  insight  into  these  condi- 
tions can  only  be  obtained  when  the  etiology  of  the  disease  has  been  estab- 
lished. One  fact  which  I  have  demonstrated  repeatedly  appears  worthy  of 
mention :  even  high  temperatures  may  not  be  influenced  in  the  slightest  degree 
by  extremely  profuse  hemorrhages  from  internal  organs  (kidney,  lungs,  in- 
testines). 

In  a  case  of  intermittent  fever  with  temperatures  up  to  102.2°  F.  which 
Kaltenbach  observed  for  a  long  time,  defervescence  occurred  by  lysis.  The 
case  was  not  a  typical  one.  Sudden  appearance  of  high  temperature  is  always 
suspicious,  and  points  to  the  existence  of  some  complication. 

Hemorrhages  from  internal  organs  are,  in  the  main,  rare;  apart  from  the 
likewise  quite  rare  epistaxis,  renal  hemorrhages  occasionally  occur  as  the  ex- 
pression of  a  recent  hemorrhagic  nephritis;  very  scanty  hemorrhagic  casts 
with  normal  and  abnormal  red  blood-corpuscles  in  the  urine  determine  the 
diagnosis.  The  amount  of  albumin  in  such  cases  is  always  very  great.  Be- 
sides the  hemorrhagic  form  of  nephritis,  we  may  also  see  during  the  course  of, 
and  in  immediate  connection  with,  the  disease,  a  nephritis  without  hemor- 
rhagic constituents.  This  form  very  frequently  gets  well ;  in  rare  cases,  how- 
ever, it  may  lead  to  edema  and  uremia. 

Pulmonary  hemorrhages  rarely  occur  in  persons  with  previously  healthy 
lungs.  If  it  is  certain  that  hemorrhagic  sputum  is  present,  the  first  assump- 
tion should  be  that  the  blood  may  come  from  the  bronchi.  Among  other  hem- 
orrhages which  are,  however,  most  uncommon,  I  must  mention  meningeal  and 
cerebral  hemorrhages. 

Regarding  the  condition  of  the  spleen  but  very  little  can  be  said ;  it  is  cer- 
tain that  in  some  cases  distinct  enlargement  has  been  determined  and  the 
organ  has  been  felt  below  the  ribs  as  a  more  or  less  soft  tumor.  In  the  great 
majority  of  cases,  however,  this  enlargement  is  absent  during  the  entire  course 
of  the  disease,  even  in  the  severest  type  of  hemorrhagic  purpura  running  a 
fulminant  course. 

The  composition  of  the  blood  in  cases  of  pure  hemorrhagic  purpura  is  men- 
tioned by  some  authors  as  having  shown  a  slight  decrease  of  the  red  and  an 
increase  of  the  white  blood-corpuscles. 

Ajello  found  the  red  decreased  to  2,500,000  to  3,000,000,  while  the  specific 
gravity  of  the  blood  was  1.043.     The  erythrocytes  are  said  to  undergo  an 


MORBUS  MACULOSUS  WERLHOFII  495 

especially  rapid  regeneration  and  show  no  morphologic  changes,  except  that 
Spietschka  found  after  protracted  hemorrhages  nucleated  red-blood  cell?  with 
polychromatophilic  protoplasm.  In  two  cases  of  hemorrhagic  purpura  he 
made  frequent  blood-examinations,  counting  the  blood-corpuscles,  estimating 
the  hemoglobin,  and  staining  permanent  preparations  with  gentian  violet  and 
aurantia.  In  one  case  the  number  of  blood-corpuscles  in  the  hemoglobin  re- 
mained constant;  in  another  only  showed  transitory  variations.  In  both  cases 
after  each  severe  hemorrhage  a  conspicuously  large  number  of  erythrocytes 
showed  distinct  nuclear  staining.  Spietschka  looks  upon  these  nucleated 
blood-corpuscles  as  juvenile  forms,  and  regards  their  appearance  as  a  sign  of 
a  markedly  increased  regeneration  of  the  blood. 

In  a  child  which  died  of  anemia  following  purpura  hemorrhagica.  Billings 
found  in  the  blood  only  500,000  to  700,000  red,  4,000  while  corpuscles,  and 
17  per  cent,  of  hemoglobin:  75  to  80  per  cent,  of  the  leukocytes  showed  no 
mononuclear  forms;  no  poikilocytosis,  no  nucleated  reds.  The  blood  findings, 
in  the  absence  of  signs  of  blood  regeneration,  resembled  those  of  pernicious 
anemia. 

According  to  my  own  numerous  investigations,  the  hemoglobin  is  fre- 
quently greatly  decreased  ;  more  so  than  would  correspond  with  the  diminu- 
tion in  the  absolute  number  of  the  red  blood-corpuscles. 

Silbermann  found  in  a  case  of  Henoch's  purpura  most  of  the  red  blood- 
corpuscles  normal,  a  I'cw  containing  but  little  hemoglobin,  others  entirely  with- 
out color  ("shadow-corpuscles").  The  leukocyte-  were  numerous  and  rap- 
idly deliquesced;  the  blood-plaques  were  markedly  increased.  To  determine 
any  functional  damage  in  the  morphologically  intact  red  blood-corpuscles,  their 
properties  were  tested  according  to  the  met  hod  of  Maragliano:  1.  Alter  en- 
closure in  paraffin;  2.  After  heating:  3.  After  compression;  I.  After  mixture 
with  0.6  per  cent,  sail  solution.  The  result  of  this  investigation  was  the  follow- 
ing: In  the  fresh  Mood  examined  under  paraffin,  he  found  normal  erythrocytes 
with  few  exceptions,  and  vrery  numerous  leukocytes.  Two  hours  later,  in  the 
same  preparation,  numerous  " shadow-corpuscles "  were  seen,  many  feebly 
stained  red  blood-discs,  and  a  few  microcytes ;  the  majority  of  the  while  blood- 
corpuscles  were  destroyed.  In  their  place  there  was  found  a  granular,  grayish 
white  heap.  Five  hours  after  the  enclosure  of  the  blood  in  paraffin  but  few 
blood-corpuscles  were  to  be  -ecu.  the  majority  of  them  being  completely  de- 
stroyed. In  the  fresh,  undiluted  blood  the  red  discs  were  destroyed  by  slight 
pressure  exerted  upon  the  cover-glass  with  a  needle-,  the  same  occurred  upon 
heating  of  the  blood  at  30°  C.  In  0.6  per  cent.  Nad  solution  a  great  number 
of  the  red  discs  losl  color  at  once;  the  white  blood-corpusclea  were  very  soon 
destroyed,  and  formed  glassy  clumps.  In  sharp  contrast  with  the  results  just 
described  are  the  blood-findings  during  the  days  of  the  disease  when  the  patient 
was  still  quite  well.  In  this  blood  neither  shadows  nor  numerous  leukocytes 
are  to  be  seen,  nor  even  greatly  Increased  blood-plaques;  under  the  influences 
previously  mentioned   the  erythrocytes  -how  a  normal  resistance,   i.e.,  they 

neither  lose  color  verv  rapidly,  nor  are  many  of  them   de-t  roved. 

For  many  years   I    have  examined    minutely  the  blood   of  patient-;  attacked 

by  various  form-  of  purpura,  and  have  found  by  no  mean-  uniform  results. 


496  THE  HEMORRHAGIC  DIATHESES 

In  many  cases  very  few  deviations  from  the  normal  were  recognized,  in  many 
others  the  signs  of  anemia  were  distinctly  observed.  Anemia  is  the  sum  and 
substance  of  the  blood  changes  in  this  affection,  if  such  changes  exist  at  all. 
Microcytosis,  poikilocytosis,  numerous  pessary  forms,  a  relative  and  absolute 
decrease  of  hemoglobin,  blood-plaques  increased,  occasionally  very  much  so, 
and  profuse  cylinder-formation  in  the  blood,  such  are  the  important  changes 
which  I  have  observed.  An  increase  of  leukocytes,  a  slight  destruction  of  the 
same,  and  the  appearance  of  isolated,  nucleated  red  blood-corpuscles  are  occa- 
sionally but  by  no  means  constantly  seen.  Moreover,  the  number  of  leukocytes 
is  subject  to  extraordinarily  rapid  change.  The  many  "  pessary  forms  "  of 
red  cells  which  are  quite  frequently  found,  in  fresh  preparations  as  well  as  in 
smears  stained  with  eosin,  are  only  a  sign  of  the  scant  hemoglobin  contents 
of  the  erythrocytes,  and  it  is,  therefore,  not  remarkable  that  in  spite  of  a  nor- 
mal number  of  red  cells  the  hemoglobin  may  be  decidedly  diminished.  In  the 
investigation  of  the  fresh  blood  of  patients  who  suffered  from  purpura,  upon 
a  warm  slide  (heated  to  30°  C),  no  change  in  the  corpuscles,  either  in  the  red 
or  in  the  white,  was  perceptible ;  they  resembled  perfectly  the  blood-corpuscles 
of  healthy  persons  or  were,  for  example,  like  those  in  malaria  patients  whose 
blood  I  had  used  for  comparison. 

TREATMENT 

Prophylaxis. — On  account  of  the  spontaneous  and  unexpected  appearance 
of  purpura  there  can  be  no  question  of  prophylaxis.  The  frequency  of  re- 
lapses should  be  a  warning  to  those  who  have  recovered  once  or  repeatedly 
from  the  disease,  to  protect  themselves  for  a  long  time  against  deleterious 
external  influences,  particularly  chilling  the  body.  Change  of  climate  has 
proven  very  beneficial. 

General  Treatment. — The  patient  must  remain  in  bed  for  a  long  time,  even 
if  no  fever  is  present.  The  more  rigidly  this  rule  is  adhered  to,  the  more 
certainly  will  relapses  be  prevented.  He  is  to  move  about  just  as  little  as 
possible.  The  more  experience  I  have  with  cases  of  this  kind,  the  more  thor- 
oughly I  am  convinced  of  the  great  value  of  rest  in  bed.  The  absolute  neces- 
sity of  this  must  be  impressed  upon  the  patient,  so  that,  from  conviction  and 
not  merely  to  please  his  plrysician,  he  will  submit  and  adhere  to  this  very 
tiresome  regime.  Every  arrangement  must  be  made  for  the  patient's  comfort 
during  this  prolonged  rest  in  bed;  he  should  be  taken  down  into  the  garden, 
or  upon  a  shady  veranda,  balcony,  or  the  like.  Further,  the  nurses  must  see 
that  no  part  of  the  patient's  body  is  subjected  to  external  pressure,  and  that 
he  does  not  bruise  or  injure  himself.  With  this  end  in  view  his  bed  must  be 
very  carefully  prepared.  Above  all,  folds  in  the  bed  sheets  must  be  prevented. 
The  covering  is  to  be  light,  the  sick  room  to  be  kept  cool.  Psychical  excite- 
ment and  mental  exhaustion  are  to  be  strictly  avoided  under  all  circumstances. 

The  nutrition  must  be  bland.  All  foods  are  to  be  given  cool.  Strong 
coffee,  tea,  and  alcohol  are  prohibited;  only  with  symptoms  of  collapse  may 
the  latter  be  made  use  of.  Of  foods,  milk  is  most  important,  perhaps  mixed 
with  somatose.     Lemonade  or  orangeade  may  be  used  as  a  drink. 


MORBUS  MACULOSUS  WERLHOFII  497 

It  is  important  that  attention  be  paid  to  the  fecal  discharges  on  account  of 
possible  hemorrhages  and  intestinal  parasites  (or  their  ova).  In  case  of  con- 
stipation no  salines  should  be  used,  but  only  mild  vegetable  laxatives,  such  as 
castor  oil,  tamarinds,  rhubarb,  cascara  sagrada  and  others;  enemata  and  irri- 
gations of  water  may  also  be  utilized.  Laxatives  should  be  changed  frequently 
so  that  the  intestine  may  not  become  accustomed  to  a  certain  remedy. 

Special  Treatment. — 1'pon  the  authority  of  Werlhof,  sulphuric  acid  is 
given,  even  to-day,  in  the  form  of  Haller's  acid  elixir,  which  Werlhof  praised 
as  a  specific.  He  also  advised  in  purpura  decoctum  cortex  chinae  (8-10:  200, 
a  tablespoonful  every  two  hours).  The  administration  of  ergot,  of  lead  ace- 
tate, turpentine,  and  liquor  ferri  Besquichlorati  has  been  Itased  upon  the 
pathology  of  the  disease.  In  very  stubborn,  frequently  relapsing  cases,  I 
have  seen  good  results  from  arsenic  in  the  form  of  Fowler's  solution,  espe- 
cially in  combination  with  carbonated  or  warm  baths  rich  in  salt.  I  can 
highly  recommend  this  treatment,  particularly  in  the  cases  in  which  all  other 
methods  have  been  without  result. 

Henoch  has  used  ergot  in  the  following  manner : 

I£   Ext.  secal.  cornut 1.5 

Aq.   destill 150 

M.,  1»..  S. :  For  children  a  teaspoonful,  for  adults  a  tablespoonful,  every 
three  hours. 

I  cannot  so  strongly  recommend  this.  Liquor  ferri  sesquichlorati  may  be 
given  in  gruel,  from  one  to  five  drops  three  times  daily. 

The  following  medication  is  also  advised,  although  I  have  never  seen  any 
results  from  it:  Twenty  to  thirty  drops  of  the  fluid  extract  of  hydrastis  cana- 
densis every  two  to  three  hours. 

In  peliosis  rheumatica  the  employment  of  sodium  salicylates,  aspirin  and 
antipyrin  is  worthy  of  trial. 

In  epistaxis,  dorsal  decubitus  with  the  head  low,  cold  to  the  nape  of  the 
neck,  and  liquor  ferri  sesquichlorati  are  indicated.  The  insufflation  of  cold 
water,  to  which  a  few  drops  of  the  previously  mentioned  iron  salt  are  added, 
will  often  control  the  hemorrhage.  Tampons  of  cotton  dipped  in  the  iron 
solution  may  also  1»'  accessary.  Gastric  and  intestinal  hemorrhages  are  to  1"' 
combated  by  ice  in  combination  with  opium.  Therapeutic  requirements  are, 
however,  rarely  necessary,  as  the  condition  is  infrequent.  The  same  is  true 
of  renal  hemorrhages. 

With  Bymptoms  of  collapse,  stimulants  are  to  be  used  (wine,  coffee  with 
brandy,  champagne,  camphor,  ether).    The  application  of  beat   may  become 

necessary  (bot  bottle-,  bot  sand  bags).     In  severe  cases  hypoden lysis  of 

physiologic  sail  solution,  to  winch  oxygen  has  lately  been  added  with  success, 
may  be  resorted  to. 

During  convalescence  the  patient   mu-t   be  placed  on  a  nourishing  diet. 

Residence  in  the  country,  by  the  sea,  or  in  the  mountains  is  advisable.     Of 

drugs,  iron  is  the  best.     Tbc  urine  is  to  be  frequently  examined  even  after  the 

actual  disease  has  run  it-  course,  for  sometimes  in  immediate  sequence  or  a 

3:j 


498  THE  HEMORRHAGIC  DIATHESES 

long  time  afterward  (weeks  and  months)  albuminuria  may  appear.  Occasion- 
ally this  disappears  with  a  stimulating  diet  and  warm  baths ;  in  other  cases  it 
remains  and  passes  into  a  chronic  (interstitial)  nephritis.  For  the  treatment 
of  this  condition,  the  article  upon  renal  disease  may  be  consulted ;  but  I  may 
remark  here  that,  even  in  such  cases,  I  have  seen  favorable  results  from  cold 
sea  baths,  though  only  in  well-nourished  and  robust  individuals. 


THE    ANIMAL    PARASITES 


THE    ANIMAL    PARASITES    OF    MAN 
By   E.    PEIPER,  Greifswai.o 

By  "  animal  parasites  of  man  "  we  mean  the  organisms  which  live  tempo- 
rarily or  permanently  on  or  in  the  hody  of  man  and  derive  their  nourishment 
from  it.  There  is  no  difference,  properly,  between  animals  that  live  as  para- 
sites and  those  that  live  free.  For,  on  the  one  hand,  there  are  parasites — e.  g., 
the  ascaris  nigrovenosa  (this  species,  indeed,  does  not  live  on  man) — which 
produce  mature  offspring  capable  of  living  free,  and,  on  the  other  hand,  ani- 
mals winch  usually  live  free  may  appear  as  parasites.  Thus,  the  larva?  of 
flies,  which  usually  live  on  decaying  organic  substances,  are  found  "  occasion- 
ally "  as  parasites  in  man,  either  in  the  intestinal  canal  or  in  suppurating 
wounds.  These  occasional  parasites  must  not  be  classed  with  the  so-called 
"  pscudoparasitcs."  By  the  latter  we  generally  mean  foreign  bodies  of  various 
kinds  ami  origin  which  are  manifest  per  vias  naturales. 

As  stated,  we  distinguish  between  a  temporary  and  a  permanent  parasitism. 
Fleas  and  bed-bugs  infest  man  only  transiently.  The  development  of  these 
organisms  is  independent  of  the  human  body.  Temporary  parasites  include 
the  ectoparasites  (or  epizoa)  which  inhabit  the  skin,  the  conjunctiva]  sac  the 
mouth,  the  nose  and  it-  accessory  cavities.  It  is  true,  the  ectoparasites  also 
include  some  permanent  parasites.      Mosl  of  the  permanent  or  stationary  para- 

-  are  found  as  entoparasites  or  entozoa  in  the  internal  organs:  in  the  intes- 
tinal canal  and  the  glands  belonging  to  it.  in  the  lungs,  in  the  heart,  in  the 
brain,  and  in  the  muscles.  Bui  the  permanent  parasites  are  qoI  all  entopara- 
Bites,  for  many  of  them  live  also  on  the  skin.  Lice  and  sarcoptes  hominis 
rarely  leave  the  body  of  man  upon  which  they  develop  from  the  ova  and 
multiply. 

.Many  parasites,  Buch  as  tenia,  ascarides,  and  ankylostoma  inhabit  man 
only  when  mature;  others,  such  as  the  echinococcus,  only  during  a  certain 
period  of  it-  development.  Man.  therefore,  is  either  the  actual  host  or  only 
the  intermediate  host.  For  many  parasites,  Buch  a-  tenia  Bolium  and  tenia 
Baginata,  man  has  the  doubtful  honor  .,1'  being  the  only  host     But,  man  also 

becomes  the  bosl  of  parasites  which,  a-  a  rule,  -elect  another  host  animal. 
Thus,  the  Cysticercus  cellulosae  occur  not  only  in  the  pig,  deer,  and  cat.  but 
by  aiitoinfcction  also  in  man.     I'.alant id iiim  coli  and  echinorhyncus  gigas  are 

specilic  parasites  of  the  pig,  but  occasionally  they  are  found  in  man. 

Since  remote  times  physicians  and  zoologists  have  attempted  to  ascertain 
the  origin  of  the  parasites.  As  a  rule,  this  has  I d  easy  with  the  ectopara- 
sites; hut  e\c lingly  difficult  with  the  entoparasites.     For  not  only  in  the 

501 


502  THE  ANIMAL  PARASITES  OF  MAN 

intestine,  but  in  the  organs  of  the  human  body  that  are  beyond  the  reach  of 
external  contact,  parasites  are  found  whose  origin  baffles  conception,  and  most 
remarkable  suppositions  and  opinions  have  arisen  regarding  this  origin.  The 
most  simple  and  most  natural  explanation  of  this  secret  of  nature  was  the 
assumption  of  a  generatio  cequivoca.  It  was  believed  that  spontaneous  gen- 
eration, which  was  supposed  to  be  common  among  the  lower  animals,  occurred 
also  among  the  entoparasites.  Endeavors  were  made  to  demonstrate  that  the 
parasites  developed  from  the  intestinal  mucus,  from  inspissated  fecal  masses, 
and  from  decomposed  blood.  Step  by  step,  the  proof  was  slowly  furnished 
that  not  only  highly  organized  animals,  but  also  the  lower  were  endowed  with 
sexual  powers,  and  that  the  parasites  developed  only  from  fecundated  ova.  In- 
vestigators have  had  to  contend  with  one  great  difficulty,  namely,  the  occur- 
rence of  young,  asexual  forms,.  But  the  transition  of  these  into  intermediate 
hosts,  their  return  to  the  specific  host,  and  their  development  into  mature  forms 
was  finally  established  experimentally. 

With  certain  exceptions,  sexual  maturity  and  parasitism  coincide  for  those 
entoparasites  which  are  under  discussion.  The  ova  or  embryos  of  the  mature 
parasites  reach  the  outside  world,  and  here,  protected  by  a  covering  which  is 
very  resistant  to  external  influences,  they  continue  their  development,  and 
finally  reach  an  intermediate  host.  Many  exceptions  occur.  The  embryos  of 
the  trichina  spiralis  pass  from  the  intestinal  wall  of  the  host  immediately  into 
his  tissues.  Others,  slipping  from  the  sac  of  the  ova,  live  free  for  some  space 
of  time;  still  others  migrate  directly  into  the  final  host,  there  to  reach  their 
maturity.  Asexual  forms  first  pass  into  an  intermediate  host,  where  they  are 
harbored  and  still  further  developed,  until  at  last  they  reach  their  final  host; 
or,  after  the  lapse  of  some  time,  they  become  subject  to  retrogressive  changes. 

Our  knowledge  of  the  distribution  of  the  animal  parasites  in  man  is  very 
incomplete.  It  is  certain  that  oxyuris,  ascaris  and  trichocephalus,  as  well  as 
the  ectoparasites,  pediculus,  cimex  and  pulex,  are  found  throughout  the  world, 
and  are  probably  the  most  common  animal  parasites.  Others,  such  as 
echinococcus,  ankylostoma,  filaria,  are  observed  only  in  certain  countries,  out- 
side of  these  only  sporadically,  and  then  introduced  from  infected  districts. 
Precise  statistical  reports  regarding  the  distribution  of  the  parasites,  which 
might  assist  in  the  explanation  of  various  questions,  are  very  limited  in 
number. 

Aside  from  the  influence  of  climate  and  soil,  the  frequency  of  the  occurrence 
of  parasites  in  man  is  due  also  to  the  customs  and  habits  of  a  country,  and, 
no  less,  to  the  personal  cleanliness  of  the  individual  inhabitants.  I  do  not 
refer  merely  to  ordinary  cleanliness  of  the  body,  which  is  of  importance  in  the 
transmission  of  the  ectoparasite,  but  particularly  to  cleanliness  in  kitchen  and 
household.  There  can  be  no  doubt  that  the  majority  of  the  parasites  are  trans- 
mitted by  food  and  drink,  by  ingestion  from  contaminated  vessels,  soiled 
hands,  etc.  In  countries  where,  as  in  Abyssinia,  beef  is  eaten  raw  or  at  least 
not  sufficiently  well  cooked,  the  beef  tape- worm  is  greatly  disseminated.  The 
tenia  solium  is  not  rarely  found  in  Central  Germany,  where  raw  or  half-cooked 
pork  is  often  eaten.  For  the  same  reason  endemics  and  epidemics  of  trichinosis 
have  not  yet  been  completely  exterminated  in  these  districts.    The  intake  of  the 


THE  ANIMAL  PARASITES  OF  MAX  503 

flukes  need  not  necessarily  be  with  measly  meat;  it  may  be  brought  about  by 
secondary  conditions.  It  is  impossible  to  enumerate  all  the  accidental  ways  by 
which  the  flukes  may  be  transmitted  to  food,  especially  in  butcher  shops  and 
restaurants  in  which  proper  cleanliness  is  lacking.  The  transmission  of  the 
bothriocephalic  latus  occurs  in  a  manner  similar  to  that  of  the  cysticerci,  the 
hooklets  of  which  are  shown  to  retain  great  vitality  in  smoked  or  frozen  pike. 

The  role  assumed  by  insects,  especially  the  common  house-fly,  in  the  dis- 
semination of  parasites  is  very  interesting.  Grassi  has  shown  that  the  ova 
of  the  tenia  solium,  oxyuris  vermicularis,  and  trichocephalus  dispar,  pass 
through  the  intestine  of  the  fly  without  change.  But  Stiles  reports  that  the 
ova  of  ascarides  undergo  further  development  in  the  intestinal  canal  of  the  fly. 
Owing  to  the  very  general  prevalence  of  flies  and  their  habit  of  settling  upon 
various  food— tuffs,  on  which  they  defecate,  there  can  be  no  doubt  that  these 
insects  contribute  materially  to  the  distribution  of  the  ova  of  the  helminthes. 
It  is  certain  that  vegetables  of  various  kinds  and  sources,  if  not  thoroughly 
washed,  or  if  eaten  raw.  may  become  the  carriers,  the  same  as  meat  if  it  has 
but  come  in  contact  with  the  ova  of  helminthes. 

We  know,  from  the  interesting  observations  of  Lutz,  how  the  ascarides  de- 
velop. The  rural  population  especially,  and,  above  all,  the  children  by  play- 
ing upon  infected  soil,  acquire  the  embryos  of  the  ascaris  lumbricoides  from 
the  soil,  whereas  the  parasites  are  far  less  frequent  among  city-bred  people, 
even  among  the  children.  The  affection  is  often  transmitted  by  food  con- 
taminated with  infected  earth,  often  by  moan-  of  the  drinking-water  into 
which  germs  capable  of  development  have  lodged. 

The  role  of  drinking-water  in  the  distribution  of  the  entoparasites  is  un- 
doubtedly of  groat  importance.  I  do  not  refer  only  to  the  transmission  of 
occasional  parasites,  but,  above  all,  to  the  protozoa,  the  ova  of  ascaris  and  of 
trichocephalus,  especially  the  immature  forms  of  the  trematodes,  winch  reach 
the  human  intestinal  canal  by  polluted  drinking-water.  Water  has  an  influ- 
ence  also  in  the  developmenl  and  distribution  of  the  ankylostoma  duodenale, 
as  we  Bhal]  see  later.  Since  the  investigations  of  Loos,  it  can  do  Longer  be 
doubted  thai  the  Last-named  parasite  is  able  to  force  its  way  into  the  human 
organism  through  the  uninjured  sJcin.  A  number  of  authors  believe  this  true 
also  of  the  filiaria  medinensis  (guinea  worm).  So  manifold  are  the  way-  in 
which  the  young  form-  of  the  parasites,  or  the  parasites  themselves,  migrate 
into  man  that  we  cannot  enter  upon  them  here. 

When  we  endeavor  to  ascertain  whence  the  runner  originate,  we  note  that 
the  majority  of  parasites  are  derived  from  animals,  especially  from  our  domes- 
tic animals,  dogs,  cat-,  pigs,  and  cattle.     I   refer  only  \>>  the  group  of  the 

cestodes,    to   the   trichina,    and    t<>    numerous   epizoa.      The    more    intimate    the 

relations  between  animal  and  man.  the  greater  the  danger  of  transmission. 
Furthermore,  man  himself  is  often  not  only  the  carrier,  hut  the  disseminator 
of  the  parasites.  Nol  only  does  he  infect  hi-  surroundings  with  the  jroung, 
hut  occasionally  he  infect-  himself,  a-  -hall  he  demonstrated  later  in  the  dis- 
cussion  of  oxyuris  vermicularis. 

In  regard  t<>  the  symptomatology,  then'  i-  perhaps  no  realm  of  pathology 
in  which  bo  many  contradictory  opinions  have  been  expressed  a-  have  been 


504  THE  ANIMAL  PARASITES  OF  MAN 

called  forth  by  the  animal  parasites,  especially  by  the  entozoa.  Formerly,  when 
certain  morbid  phenomena  could  not  be  explained,  enigmatical  symptoms  were 
ascribed  to  the  accidental  presence  of  one  or  several  parasites,  thus  giving  rise 
to  many  vague  conceptions;  later  there  was  an  evident  inclination  to  ascribe 
little,  or  no,  reaction  upon  the  affected  organism  to  animal  parasites,  espe- 
cially to  the  entozoa.  Undoubtedly,  both  tendencies  were  wrong.  The  phe- 
nomena observed  in  many  persons  infected  by  parasites,  especially  the  nervous 
manifestations,  cephalalgia,  pruritus,  disturbances  of  sight  and  hearing, 
mydriasis,  sensations  of  general  weakness  and  lassitude,  should  not  always  be 
regarded  as  the  consequence  of  helminthiasis.  The  decision  regarding  the 
causal  connection  depends  also  upon  whether  the  symptoms  have  occurred  only 
after  the  appearance  of  the  parasite  and  have  ceased  soon  after  the  expulsion 
of  the  unwelcome  visitor.  Thus,  Cobbold  and  Davaine  report  a  number  of 
cases  in  which  various  nervous  symptoms  disappeared  after  the  expulsion  of 
a  tape-worm.  In  a  case  of  epilepsy  which  had  persisted  for  three  years  Marx 
saw  a  cure  take  place  after  the  expulsion  of  tenia  solium.  In  a  patient  who 
suffered  from  tabetic  phenomena,  and  in  whom  there  was  marked  temporary 
myosis  and  loss  of  the  pupillary  reaction,  Denti  noted  that  alb  symptoms  were 
cured  by  the  expulsion  of  a  tenia  solium.  Noticeable,  too,  are  the  frequent 
reports  of  disturbances  of  the  visual  apparatus  in  helminthiasis.  In  short,  it 
is  certain  that  considerable  disturbance  of  health,  sometimes  even  serious  dan- 
ger to  life,  may  be  caused  by  the  presence  of  parasites. 

It  is  obvious  that  delicate,  nervous,  anemic  persons  suffer  much  more  from 
the  presence  of  parasites  than  robust  individuals,  whose  power  of  resistance  is 
greater,  and  that  the  reaction  in  the  former  is  much  more  violent.  The  with- 
drawal of  food-stuffs  which  are  easily  assimilated  but  which  often  cause  the  ex- 
pulsion of  the  tape-worm  chains,  meters  in  length,  or  numerous  ascarides  from 
the  intestinal  canal,  must  inevitably,  apart  from  the  local  reaction,  be  fol- 
lowed by  injurious  sequels,  especially  in  weak  persons  and  children.  The 
presence  of  hundreds,  even  thousands,  of  blood-sucking  ankylostomata  cannot 
fail  to  produce  serious  disturbances.  Parasites  which  have  lodged  in  vital 
organs,  in  the  liver,  lungs,  heart  and  in  the  eyes,  in  the  brain  and  the  spinal 
cord,  even  if  relatively  small,  will  certainly  cause  serious  functional  disturb- 
ances and  disease. 

The  investigations  in  the  last  decade  by  Eeyher,  Euneberg,  Dehio,  Scha- 
piro,  Schaumann,  and  others,  have  demonstrated  that  the  animal  parasites, 
especially  the  bothriocephali,  produce  toxins  which,  taken  into  the  blood,  may 
lead  to  the  severe  manifestations  of  pernicious  anemia.  The  secretion  of  toxic 
substances  by  other  animal  parasites,  such  as  echinococci,  ascaris  lumbricoides, 
ankylostoma  duodenale,  etc.,  is  also  probable.  We  do  not  as  yet  know  the  toxin 
itself,  but  we  recognize  its  deleterious  effects. 

The  number  of  parasites  occurring  in  man  is  very  large.  Every  year  fur- 
nishes reports  of  the  appearance  of  animal  parasites  until  then  unknown.  In 
the  following  I  shall  review  the  fauna  of  man.  It  seems  most  practicable  to 
discuss  them  in  a  systematic  order.  I  begin,  therefore,  with  those  organ- 
isms which  can  only  with  difficulty  be  separated  from  the  lowest  vegetable 
organisms. 


PROTOZOA 


505 


PROTOZOA 

We  designate  as  protozoa  the  primordial  animals,  those  microscopically 
small  but  living  organisms  which,  as  monocellular  elements,  singly  or  in  colo- 
nies, collectively  represent  the  simplest  animal  type.  The  substance  of  the 
body,  sarcode,  consists  of  a  contractile,  finely  granulated  protoplasm  which  is 
mononuclear  or  polvnuclear.  The  viscid,  hyaline  ectosarc  is  capable  of  motion 
by  contraction  and  expansion,  or  by  extension  and  retraction  of  pseudopodia, 
by  cilia  and  flagella.  There  can  be  no  doubt  that  it  is  concerned  in  the  inges- 
tion and  excretion  of  food.  Fissures  and  openings  in  the  ectosarc  take  the 
place  in  some  protozoa  of  the  functions  of  mouth  and  anus.  The  soft  endo- 
sarc  serves  for  the  digestion  of  the  food  consumed;  the  contractile  vacuoles, 
occurring  in  many  protozoa,  are  intended  for  the  accumulation  of  fluids  to  be 
excreted.     Propagation  takes  place  by  segmentation,  gemmation  or  sporulation. 

We  know  that  all  three  varieties  of  the  protozoa,  the  rhizopoda,  the  sporozoa 
and  the  infusoria,  occur  as  parasites  in  man. 

The  rhizopoda,  "root-footed"  organisms,  include  the  amoeba  coli  (Loesch), 
discovered  in  1875,  the  amoeba  coli  felis  of  Quincke  in  is!»:?,  the  amoeba  coli 
mitis  of  Quincke,  which  is  minutely  described  in  the  interesting  treatise  of 
Hoppe-Seyler,  "  Dysentery  and  Ameba  Enteritis/'  1  and  the  amoeba  coli  vul- 
garis of  Quincke.  The  investigations  of  Quincke  and  Roos  have  proven  that 
the  latter  are  not  pathogenic  cither  in  man  or  in  cats.  The  severe  and  well- 
known  dysenteric  symptoms  caused  by  the  first-named  ameba  may  be  mate- 
rials complicated  by  the  supervention  of  liver  abscesses.  Cases  of  infection 
by  amoeba  coli  mitis  are  considerably  milder,  but  of  a  distinctly  chronic  course. 
lor  details  regarding  these  parasites  I  refer  to  the  previously  mentioned  article. 

Ameba?  in  man  are  not  confined  to  the  intestines.  I  have  referred  to  their 
occurrence  in  the  pus  of  liver  abscesses  in  dysentery.     Jjima  demonstrated 


•  .if   '  .V   ***. 


Flo.  27.— Ambra  m 
M>>i  ion. 


Fig.  28. — Ami  v.\   I  I  \  r- 

II  \  I  D. 


Fig.  2<i       \mi  B  v  at 

Mi  - 1 . 

In.-    •_'<;  2s. —  I.kydkviv  Gemmipaba.     (After  von  Leyden-Schaudinn.) 
a,  nucleus;  <.  vacuole;  /"',  pulsating  vacuole. 


amebse  in  pleuritic  and  peritoneal  exudates.  Groa  and  Sternberg  have  reported 
the  presence  of  amebae  in  the  tartar  of  the  teeth.  Flexner  found  amebs  in  an 
abscess  in  the  oral  cavity,  ELartulia  in  the  pus  and  in  an  extra. ted  portion  of 


i  Bee  the  chapter  on  Dysentery  En  volume,  "  [niectiotu  Di» 


506  THE  ANIMAL  PARASITES   OF  MAN 

the  lower  jaw.  Baclz  observed  amebse  in  the  urine,  Jürgens  in  the  mucous 
membrane  of  the  bladder,  Kartulis  in  a  tumor  of  the  bladder,  Wijnhoff  and 
Zeehuisen  in  nmeohemorrhagie  urine,  and  their  causal  relation  to  the  morbid 
phenomena  is  not  }ret  explained.  This  detection  of  amebae  is  undoubtedly  very 
interesting,  but  a  definite  opinion  regarding  their  significance  cannot  be 
arrived  at  until  the  culture  of  amebas  in  pure  culture  has  been  accomplished. 
Then  Ave  shall  be  able  by  experiments  to  estimate  their  true  significance  as 
generators  of  disease. 

v.  Leyden  and  Schaudinn  found  in  the  ascitic  fluid  of  two  cases  of  carci- 
noma structures  of  an  irregular  polygonal  or  globular  form,  which,  in  a  con- 
tracted condition,  measured  from  3  to  36  fi.  Uncontracted,  they  possess  the 
power  of  ameboid  movement,  and  send  forth  processes  which  are  either  hyaline 
or  lamellar  or  granular.  The  plasma  is  thickly  studded  with  very  refractive 
granules  of  a  yellowish  luster.  Several  vacuoles  for  fluid,  among  them  one 
pulsating,  are  generally  found,  and  one  nucleus.  Propagation  occurs  by 
gemmation  and  segmentation.  Similar  structures  were  found  by  Lauenstein 
and  Behla  in  the  ascitic  fluid  of  patients  with  carcinoma.  It  is  still  unde- 
cided whether  the  Leydenia  gemmipara  Schaudinn,  1896,  has  any  relation 
to  carcinoma. 

The  second  class  of  the  protozoa,  the  sporozoa,  includes  parasites  which 
have  also  been  discussed  by  the  above-mentioned  authors,  such  as  the  coccidium 
oviforme,  Leuckart,  1879,  the  coccidium  perforans,  Leuckart,  1879,  and  the 
coccidium  bigemimum,  Stiles,  1891.  These  parasites  are  rarely  found  in  man, 
it  is  true,  but,  when  present,  they  cause  obstinate  intestinal  catarrhs  which  are 
difficult  to  cure.  Undoubted  cases  of  coccidiosis  of  the  kidneys  and  of  the 
ureters  have  also  been  described  by  Lindemann,  Bland-Sutton,  and  Targeff. 
In  the  case  reported  by  Clarke  numerous  small,  greenish-brown  cysts  contain- 
ing the  parasites  in  varying  sizes  were  found  in  the  renal  pelvis,  in  the  ureters, 
and  in  the  bladder. 

Miescher's  or  Bainey's  tubes,  which  became  known  from  the  microscopical 
examination  of  pork,  are  of  no  pathogenic  significance  and  are  only  rarely 
found  in  man.  Apart  from  the  doubtful  cases  of  Lindemann  and  Eosenberg, 
such  structures  have  been  found  in  man  only  by  Kartulis  in  the  muscles  of 
the  abdomen,  and  by  Baraban  and  Saint-Bemy  in  the  muscles  of  the  larynx. 

The  most  important  group  of  the  sporozoa  are  the  hemosporidia  which 
include,  as  is  well  known,  the  malarial  parasites  of  man.  The  highly  interest- 
ing history  of  the  development  of  these  parasites,  and  also  the  pathological  con- 
dition produced  by  them,  have  been  exhaustively  discussed  in  the  chapter  on 
Malaria  (which  see  in  volume  "  Infectious  Diseases  "). 

In  concluding  this  study  of  the  sporozoa,  I  desire  to  mention  that  in  the 
future  we  may  possibly  be  able  to  attribute  other  parasitic  affections  of  man  to 
the  parasitic  nature  of  the  protozoa.  Some  well-known  authors  assume  that 
the  pathogenic  germs  of  carcinoma,  sarcoma,  scarlatina,  measles,  smallpox,  per- 
tussis, etc.,  are  represented  by  certain  protozoa  yet  to  be  found  or  to  be  inves- 
tigated. Unfortunately,  the  researches  undertaken  up  to  the  present  have  not 
led  to  a  positive,  indisputable  result. 

The  third  class  of  the  protozoa  embraces  the  infusoria,  which  are  structures 


PROTOZOA 


507 


of  more  or  less  constant  form,  and  covered  with  cilia  in  varying  number  and 
arrangement.     The  infusoria  include  the  flagellates  and  the  ciliated  parasites. 

Of  the  flagellates,  trichomonas  vaginalis,  Donne,  1837,  is  frequently  found 
in  yellowish,  markedly  acid  vaginal  mucus,  whereas  the  parasite  is  not  pres- 
ent in  the  normal  secretion  of  the  vagina.  The 
parasite,  which  is  elliptical  in  shape,  and  0.01 
nun.  in  length,  is  elongated  into  a  delicate  process 
at  the  anterior  border  of  which  there  are  usually 
four  long,  slender,  whip-like  flagella.  An  undu- 
lating membrane,  the  contracting  wave  of  which 
is  continually  directed  anteroposteriorly,  extends 
spirally  from  the  point  of  origin  of  the  flagella. 
The  parasite  was  found  in  purulent  urine  by 
Marchand,  Miura  and  Dock;  in  human  feces  by 
Janowski  and  Skalier;  in  the  contents  of  the 
stomach  in  carcinomas  cardiae  by  Strube.  It  also 
appear-  thai  the  flagella  found  by  Davaine,  Grassi, 
Eckekrantz,  Cunningham,  Tham,  Marchand,  Zun- 
ker,  Epstein,  May,  Roos,  Schuberg,  Schürmayer, 
and  others,  which,  following  Davaine  (1854),  are 
designated  as  trichomonas  hominis,  are  no1  essen- 
tially different  from  trichomonas  vaginalis.  Simi- 
lar structures  were  also  found  in  the  -put urn  in 
gangrene  of  the  lungs  by  Kannenberg,  Streng  and 
Schmidt,  in  serous  pleural  exudate  by  Litten,  in 
putrid  pleurisy  by  Roos.  It  appears  that  the  para- 
site designated  plagiomonas  urinaria  by  Künstler, 
in  1883,  also  belongs  in  this  class.  The  cilia 
observed   by  earlier  authors  were  probably   only 

simulated  by  the  continuous  motion  of  the  undulating  membrane.    The  num- 
ber of  the  flagella  is  by  qo  means  characteristic. 

\'o  positive  statements  can  be  made  regarding  the  significance  of  the  tricho- 
monades  as  generators  of  disease.  Yet  it  is  quite  conceivable  that,  if  presenl 
in  enormous  quantities,  they  might  lead  to  long-continued  suppuration  and 
catarrh  of  the  intestine.     As  a  rule,  they  are  easily  exterminated  by  repeated 

doses  of  0.1-0.2  of  calomel. 

Megastoma  entericum  Grassi,  1881,  and  s.  Lamblia  intestinalis  Lambl, 
1859,  are  of  the  same  significance.  The  exacl  description  of  this  parasite 
will  he  found  in  t  he  chapter  on  Dysentery,1  where  it  is  also  stated  that  the 
parasite,  if  occurring  in  large  numbers,  may  cause  an  intestinal  catarrh  which 
is  usually  cured  without  difficulty  unless  complicated  by  carcinoma  or  tuber- 
culosis. 

(if  other  flagella,  monas  globulus,  Dujardin;  monaslens,  Dujardin;  monas 
elongata,  Dujardin;  bodo  intestinalis,  Ehrenberg;  cercomonas  acuminata. 
Dujardin;   cercomonas   globulus,    Dujardin;   cercomonas   biflagellata,   Stein- 


Fig.  29. — Trichomonas  Vagi- 
naijs,  Donne;  Consider- 
ably Enlaikjed.  (After 
Künstler.) 


'  Volume,  "  Infectious  I  >i  . 


508  THE  ANIMAL  PARASITES  OF  MAN 

berg;  trichomonas  elongata,  Steinberg;  trichomonas  caudata,  Steinberg;  and 
trichomonas  flagellata,  Steinberg,  have  been  probably  found  as  simple  com- 
mensals. 

Of  the  cilia  inhabiting  man,  cilia  infusoria,  we  are  most  interested  in  the 
balantidium  coli,  Malmsten,  1857,  the  pathogenic  significance  of  which  as  the 
generator  of  severe  dysenteric  intestinal  catarrhs  is  also  described  in  the  chap- 
ter on  Dysentery.  Stockvis  has  also  found  balantidia  in  the  sputum  of  a  sol- 
dier who  had  returned  from  the  Sunda  Islands. 

Jacoby  and  Schaudinn  have  recently  found  a  new  balantidium  minutum 
n.  sp.  in  diarrheic  stools,  and  also  the  nyctotherus  faba  n.  sp.,  illustrations  of 


Fig.  30. — Balantidium  Minutum.  Fig.  31. — Nyctotherus  Faba. 

n,  nucleus;  cv,  contractile  vacuole.     (After  mi.n,  micro  nucleus;  ma.m,  macronucleus. 

Schaudinn.)  (After  Schaudinn.) 

which  follow.  Vorticelli,  which,  according  to  Lindner,  are  said  to  infest  man, 
cannot  yet  be  recognized  as  parasitic  structures. 

This  embraces  the  principal  protozoa  which  occur  in  man. 

We  now  come  to  the  more  highly-organized  class,  the  plathelminthes  or 
flat-worms.  To  this  group,  which  embraces  the  two  classes  of  trematodes,  or 
sucking-worms,  and  cestodes,  or  tape-worms,  belong  the  "  vermes  intestinalis  " 
of  the  earlier  authors  or  "  helminthes  "  which — sit  venia  verbo — represent  the 
true  intestinal  worms. 

TREMATODES 

The  tongue-  or  leaf-shaped  trematodes  include  the  amphistomum  hominis, 
Lewis  and  McConnell,  1876. 

I  wish  to  include  this  parasite  for  the  sake  of  completeness.  Observed 
but  a  few  times  in  the  tropics,  it  possesses  no  actual  interest  for  us,  especially 
since  its  significance  as  a  parasite  is  by  no  means  accurately  determined. 

Of  greater  importance  is  the  distomum  hepaticum,  Linne,  1758. 

The  liver-fluke  is  found  in  the  intestines  and  in  the  bile-ducts  of  a  great 
number  of  mammals,  especially  in  the  sheep.  Eot  or  liver  disease  in  many 
districts  creates  great  ravages  among  sheep.  The  parasite  is  also  often  noted 
to  occur  sporadically.  Its  body  is  oblong,  flat,  leaf-like,  with  a  proboscidiform 
projection  on  the  cone-shaped  head.  One  of  the  two  suctorial  discs  is  situ- 
ated at  the  point  of  the  cone-like  head,  and  contains  the  opening  of  the  mouth. 
The  other  suctorial  disc  belongs  to  the  abdominal  surface.     The  oval  eggs  are 


TREMATODES 


509 


Fig.  32. — Distomfm 
Hepaticum,  Linne. 


of  a  considerable  size:  Breadth  0.075  to  0.09  mm.,  length  0.14  to  0.15  mm. 
The  anterior  pole  is  flatter  and  has  a  lid. 

The  development  of  the  liver-fluke,  explained  by  Leuckart  and  Thomas,  is 
a  very  complicated  one.  The  ova  are  discharged  with  the  feces.  After  a  pro- 
longed stay  in  water,  the  elongated  miracidium  develops 
and  after  some  time  breaks  the  cover  of  the  egg.  By 
means  of  its  ciliary  sac  it  floats  about,  and  finally  is 
taken  up  by  its  first  intermediary  hosts,  small  water 
snails,  the  limmeus  minutus  and  limnaens  cahuensis, 
which  are  found  in  large  numbers  in  small  pools.  In 
this  host  the  miracidia  become  Iran-formed  into  sporo- 
cysts,  which  are  generally  found  in  the  respiratory  cavity 
of  the  snail.  The  sporocysts  produce  a  second  genera- 
tion of  germ  tubules,  redia,  from  which,  finally,  the  true 
young  of  the  distoma  develop  in  the  form  of  caudate 
cercaria.  The  cercaria  then  emerge,  adhere  to  grass  and 
«rater  plants  and.  with  these,  enter  their  final  host  in  an 
encysted  form.  From  the  intestine  they  migrate  into  the  bile-ducts,  where 
they  develop  into  mature  animals. 

It  is  obvious,  in  view  of  this  mode  of  development,  that  man  is  but  rarely 
inhabited  by  distoma,  and  even  then  only  by  a  small  number.  The  entrance 
of  the  cercaria  into  man  occurs  principally  by  their  ingestion  with  polluted 
drinking-water  or  with  raw  vegetables,  salad,  or  water-cress,  which  have  grown 
in  inundated  places.  In  many  other  ways  they  may  enter  the  body;  we  need 
only  consider  how  often  children  and  even  grown  people  put  meadow-plants  into 
the  mouth. 

About  18  cases  of  disease  of  the  liver  in  man  from  distoma  have  been  re- 
corded. As  only  very  few  parasites  were  present,  no  special  Bymptoms  were 
caused  in  the  majority  of  these  cases.  Yet  the  cases  of  Bostroem  and  Biermer, 
in  which  the  fatal  outcome  of  the  disease  was  due  to  the  parasite,  prove  that 
even  a  single  parasite  may  produce  severe  phenomena. 

It  seems  that  the  parasites  remain  latent  for  considerable  time.  The 
general  condition  of  the  patient  changes  gradually  for  the  worse,  he  ema- 
ciates, obstinate  jaundice  and  uncontrollable,  sometimes  hemorrhagic,  diar- 
rhea develop.     Then  follow  vomiting,   violent    pains  in   the  region   of  the 

liver  and  genera]  dropsy  until,  with  progressing  cachexia,  death  take-  place. 
The  autopsy  often  Bhows  numerous  changes  in  the  liver:  Enormous  dilata- 
tion and  occlusion  of  the  bile-duct-  with  ulceration  of  the  same;  excessive 
increase  of  the  connective  tissue  in  the  area  surrounding  the  focus  of  the  para- 
Bite;  obliteration  of  the  large  bile-ducts,  occlusion  of  the  hepatic  duct.  etc. 
If.  therefore,  the  diagnosis  should  be  difficult,  an  examination  of  the  stools 
will  enable  the  physician  to  recognize  the  disease.  Bostroem  and  Perroncito 
succeeded  in  finding  the  ova  of  distomata  in  the  -tools. 

Owing  to  the  difficulty  of  the  diagnosis,  the  treatment  must  always  remain 
symptomatic;  bul  it'  the  diagnosis  be  correctly  made,  the  expulsion  of  the 
liver-fluke  may  be  attempted  by  the  administration  of  mineral  water-  or  other 
remedies  pro ting  the  secretion  of  bile. 


510 


THE  ANIMAL  PARASITES  OF  MAN 


Occasionally  the  liver-fluke  may  pass  from  the  liver  into  other  organs. 
Duval  found  the  parasite  in  the  trunk  of  the  portal  vein,  and  Friedberger  in 
the  portal  vein.  It  was  found  in  abscess  cavities  upon  the  plantar  surface  of 
the  foot  by  Giesker ;  behind  the  ear,  by  Fox ;  in  the  right  hypochondriac  region, 
by  Dionis  des  Carrieres;  and  it  was  extracted  from  the  shoulder  region  by 
Malherbe.  Eaillet  reports  that  a  French  officer  in  Eio  coughed  up  a  Senegal 
liver-fluke. 

The  bile-ducts  of  various  mammals  contain,  together  with  the  distomum 
hepaticum,  the  distomum  lanceolatum,  Eudolphi,  1803,  which,  like  the  dis- 
tomum crassum  Busk,  1850,  has  been  found  but  rarely  in  man. 

Besides  these,  I  shall  also  mention  the  distomum  heterophyes,  v.  Siebold, 
1852,  and  the  distomum  ophthalmobium,  Diesing,  1850,  as  they  have  been 
rarely  observed  in  man. 

In  Formosa,  Korea,  and,  particularly,  in  Japan,  the  distomum  Wester- 
manni,  Herbert,  1878,  is  frequently  found,  and  this  is  also  designated  dis- 
tomum pulmonale,  Baelz,  1883,  distomum  Eingeri,  Cobbold,  1880. 

This  reddish-brown  parasite,  according  to  Baelz,  attains  a  length  of  8-10 
mm.,  a  breadth  of  5-6  mm. ;  it  is  oval,  slightly  rounded  at  the  ends ;  a  cross 
section  is  almost  circular;  the  suctorial  discs  of  the  mouth  and  abdomen  are 


Fig.  33. — Distomum  Westermanni  and 
Ovum.     (After  Katsurada.) 


Fig.  34. — Distomum  Spathulatum  and 
Ovum.     (After  Katsurada.) 


almost  of  equal  size.  The  ova,  thousands  of  which  are  often  found  in  bloody 
sputum,  are  of  a  brown  color,  0.08  to  0.01  mm.  long  and  0.05  mm.  broad, 
thin-shelled,  and  showing  a  lid  at  the  blunt  end.  Besides  in  man,  the  parasite 
has  been  found  in  the  dog  and  also  in  animals  of  the  cat  family,  especially  in 
Japan. 

Distomatosis  is  widely  disseminated  in  Japan,  and  is  the  cause  of  an  appar- 
ently harmless  hemoptysis.  The  parasites  are  found  in  cavities;  in  one  case 
dissected  by  Baelz  there  were  twenty  specimens.  These  cavities  contain  a 
reddish,  pulpy  mass  consisting  of  mucus,  red  blood-corpuscles  and  numerous 
distoma  ova.  The  cavities  are  connected  with  the  bronchi  by  sieve-like  open- 
ings through  which  the  ova,  sometimes  in  enormous  numbers,  reach  the  spu- 


TREMATODES  51 1 

tum.  The  patient's  general  health  is  not  materially  impaired;  but  there  is 
danger  of  fatal  hemorrhages.  The  diagnosis  is  determined  by  the  demon- 
stration of  the  ova.  The  ova  of  the  distoma  may,  according  to  Yamagiva  and 
Otani,  be  carried  to  the  brain,  and  there  give  rise  to  serious  disease. 

No  special  therapy  is  known  as  yet.  But  it  seems  advisable  that  persons 
infected  by  distoma  should  leave  the  regions  where  these  are  found  in  order 
to  avoid  further  infection. 

The  distomum  spathulatum,  Leuckart,  187G,  or  distomum  sinense,  Cob- 
bold,  1875,  is  very  common  in  man,  and  also  in  the  cat,  in  China  and  in 
some  parts  of  Japan. 

This  parasite  is  reddish,  almost  transparent,  flat.  10-18  mm.  long,  with 
pointed  anterior  and  posterior  ends;  the  skin  is  smooth.  The  suctorial  disc 
of  the  mouth  is  larger  than  that  of  the  abdomen;  the  latter  is  situated  at 
the  line  of  the  first  quarter  of  the  body.  The  oval  eggs,  0.028-0.03  mm.  long 
and  0.016-0.017  mm.  broad,  are  encapsulated,  and  gradually  become  black. 

The  parasites  are  generally  found  in  large  numbers  in  the  bile-ducts,  but 
rarely  in  the  stomach  and  in  the  intestines.  They  produce  severe  clinical 
disturbances.  According  to  Baelz,  the  trouble  begins  with  enlargement  of  the 
liver,  and  a  sensation  of  pressure  and  weight  in  its  region;  this  is  accom- 
panied by  a  morbid  appetite.  After  some  years  the  nutrition  becomes  defec- 
tive, and  uncontrollable  diarrheas  make  their  appearance  and  later  become 
hemorrhagic.  Gradually  dropsy,  ascites,  and  anasarca  develop,  and  the  pa- 
tients finally  succumb  with  severe  cachectic  phenomena.  The  autopsy  shows 
the  walls  of  the  gall-bladder  and  bile-duct  studded  with  cyst-like  sinuses  the 
size  of  a  nut.  which  often  contain  numerous  parasites.  The  sinuses  communi- 
cate with  the  bile-duets.  The  liver  is  enormously  enlarged  but  of  normal 
color.  The  tissue  in  the  neighborhood  of  the  parasitic  foci  is  atrophied.  The 
Ova  of  the  parasite-  are  always  found  in  the  feces.  We  know  hut  little  regard- 
ing the  development  of  the  parasite,  only  that  the  ovum  while  in  utero 
develops  a  ciliated  miracidium.  The  young  forms  of  the  parasite  probably 
live  in  mollusca.  In  later  stages  of  developmenl  they  must  reach  the  intestinal 
trad  of  man  with  raw  vegetable,  and  possibly  also  with  animal,  food. 

The  distomum  conjunction,  Cobbold,  1859,  has  been  found,  bo  far.  only 
twice,  in  individuals  in  India  who  had  succumbed  to  severe  dysentery. 

Distomum  felineum,  Uivolla,  lSSö,  sive  distomum  sibiricum,  Winogradoff, 
lsii'j,  deserves  special  menl  ion. 

According  to  its  contractions,  its  length  is  8-18  mm.,  and  its  breadth 
1.5-2.5  mm.  The  parasite,  according  to  Braun,  in  fresh  condition,  is  of  a 
reddish  color,  almosl  transparent,  flattened,  and  pointed  at  the  anterior  end; 
the  skin  i-  not  weaponed.  The  suctorial  discs  are  of  almosl  equal  size.  The 
pharynx  is  immediately  adjacent  to  the  suctorial  disc  of  the  mouth;  the 
esophagus  is  as  long  as  the  pharynx.  The  intestinal  -hank-,  which  do  Dot 
branch  out,  extend  to  the  posterior  end  of  the  body,  and  are  filled  with  dark 
brown,  granular  masses.  The  eggB  are  oval,  and  have  a  lid  which  is  sharply 
defined;  the  length  is  0.02  0.03  mm.,  the  breadth  0.011-0.015  mm. 

The  para-iii'  Winogradoff,  which  until  1892  was  only  found  in  the  eat.  in 

that    vear  wa-   noted   in  !,<>  a    \erv    frequenl    para-ite  of  man.   being  present    in 


512 


THE  ANIMAL  PARASITES   OF  MAN 


the  liver.  In  the  nine  cases  observed  by  Winogradoff,  death  was  not  due  to 
the  parasites.  Yet  the  changes  produced  by  it  are  quite  considerable,  viz., 
dilatation  and  inflammation  of  the  bile-ducts,  and  foci  of  cirrhosis.  In  one 
case  there  were  small  pus  foci;  jaundice  and  contraction  of  the  liver  existed 
in  five  cases,  ascites  in  three;  the  liver  was  twice  found  to  be  enlarged. 

Braun's  assumption  that,  owing  to  the  great  dissemination  of  distomum 
felineum  among  cats,  it  must  also  be  present  in  man,  was  soon  confirmed. 
Askanazy  reported  such  a  case  from  East  Prussia,  in  1900.  It  occurred  in 
a  man  who  had  died  of  colloid  carcinoma,  which  originated  in  the  epithelium 
of  the  bile-ducts.  The  microscopical  examination  revealed  ova  and  about 
100  specimens  of  distomum  felineum  in  the  regions  not  aifected  by  the  tumor. 
The  same  author  reported  a  second  case,  also  from  East  Prussia. 

Askanazy  supposes  the  infection  in  man  to  be  due,  as  in  the  cat,  to  the 
consumption  of  raw,  or  only  partially  cooked,  fish. 

Of  great  interest  is  another  trematode,  distomum  haematobium,  Bilharz, 
1852,  or  the  Bilharzia  hamiatobia,  Bilharz,  1852.     The  parasites  live  sexually 

apart.  The  male  is  thicker  (up  to  1  mm.)  and 
shorter  (12-1-1  mm.)  than  the  more  slender  (up 
to  0.13  mm.)  and  longer  female  (16-18  mm.). 
The  anterior  part  of  the  body  which  contains  the 
suctorial  discs  is  flattened.  The  posterior  part  of 
the  body  of  the  male,  by  a  turning  up  of  the 
lateral  borders,  forms  a  tube  (canalis  gynascopho- 
rus)  which  serves  for  the  reception  of  the  female. 
The  surface  of  the  male  is  covered  with  small 
spiny  warts,  that  of  the  female  is  smooth.  The 
ova,  which  are  often  found  in  large  numbers  in 
the  vagina,  are  slender  and  quite  long,  about  0.12 
mm.  long  and  0.04  mm.  broad.  They  are  pointed 
at  one  end,  or,  more  rarely,  supplied  with  a 
pointed  side  tooth.  The  shell  of  the  ova  is  thin, 
and  there  is  no  lid.  The  full  grown  parasites  are  found  in  man  in  the  portal, 
splenic  and  renal  veins,  also  in  the  venous  plexus  of  the  urinary  bladder,  and 
in  the  rectum.  The  ova  lie  in  small,  white  masses  in  the  various  organs,  espe- 
cially in  the  urinary  passages,  in  the  vesicula  seminalis,  and  in  the  mucosa 
and  submucosa  of  the  large  intestine.  The  primary  seat  of  the  ova  is  probably 
the  vascular  system.  The  ova,  deposited  in  the  veins  which  are  distended  to 
small  diverticula  enter  the  tissues  only  after  rupture  of  the  vessels. 

The  history  of  the  development  of  the  parasite  which  occurs  mostly  and 
quite  frequently  in  Africa,  and  especially  in  Egypt,  is  not  yet  clear.  We  know 
only  the  following:  The  ova  are  discharged  with  the  urine.  Sometimes  empty 
sacs  of  ova  are  found  in  the  urine  synchronously  with  free  embryos.  Evidently 
a  miracidium,  completely  ciliated,  escapes  from  the  ovum  in  urine  that  is 
greatly  diluted  with  water  and  floats  for  some  time  in  the  water.  It  appears 
likely  that  there  is  an  intermediate  host;  but  all  attempts  to  infect  mollusca, 
Crustacea,  and  fish  have  been  fruitless.  Loos  doubts  the  transmission  by  an 
intermediate  host.    The  embryo,  in  the  opinion  of  this  author,  enters  directly 


Fig.  35. — Ova  of  Distomum 
h.-ematobium. 


TREMATODES  513 

into  man,  and  develops  into  a  sporocyst  which  then  infects  a  patient  with 
its  young. 

It  has  been  assumed  that  man  becomes  infected  with  the  parasite  by  drink- 
ing infected  water.  Yet  the  observations  and  the  experimental  investigations 
of  Loos  make  this  assumption  doubtful.  Attempts  to  infect  monkeys  by 
giving  them  infected  water  to  drink  did  not  prove  successful.  Brock  and  Loos 
assume  that  the  parasites  gain  access  directly  through  the  skin  during  bathing. 
Men  and  boys  are  affected  much  more  frequently  than  women  and  girls  who 
bathe  but  rarely.  Brock  found  that  the  newly  arrived  in  the  Transvaal  who 
went  bathing  were  soon  infected,  whereas  others  who  did  not  bathe  remained 
free  from  the  parasite.  Loos  rejects,  however,  the  assumption  of  Earley  and 
Allen  that  the  parasite  finds  entrance  into  the  body  through  the  urethra. 
The  incubation  period,  according  to  Loos,  is  four  weeks;  according  to  Brock. 
four  months. 

In  addition  to  the  parasites  at  the  points  of  predilection  in  the  vascular 
system,  autopsies  reveal  the  most  marked  changes  in  the  bladder  and  in  the 
ureters.  In  freshly  developed  cases  there  is  a  marked  catarrh  of  these  organs 
with  a  viscid,  yellowish-red  mucus  in  which,  as  also  in  the  mucous  membrane 
itself,  numbers  of  distoma  eggs  are  found.  In  chronic  cases  the  mucous 
membrane  shows  the  signs  of  a  severe  chronic  catarrh,  and  has  a  sandy  ap- 
pearance. Characteristic  excrescences,  from  the  size  of  a  pea  to  that  of  a 
bean,  ami  having  the  appearance  of  hemorrhagic  ccchymoses,  are  formed  in 
the  swollen  submucous  tissue.  The  excrescences  sometimes  become  encrusted, 
and  then  represent  stony  polypi  which  are  broken  oif  and  form  the  nuclei 
of  bladder  stones.  Pyelitis,  nephritis  and  hydronephrosis  follow  in  severe 
cases.  K  a  tt  u  1  is.  Alba  nan-Bernard  and  Harrison  quote  cases  from  their  expe- 
riences which  -bow  in  the  tissues  permeated  with  distomata  the  tendency  to 
proliferation,  that  is,  to  formation  of  carcinoma.  Not  the  parasites,  but  the 
ova,  cause  the  severe  irritation.  They  are  also  found  in  the  lungs,  in  the 
liver,  in  the  prostate  -land  and  in  the  mesenteric  glands. 

Clinically  we  encounter  at  lir-t  tin'  manifestations  of  a  hematuria  asso- 
ciated with  burning  pain  in  the  urethra.  At  lir-t  intermittent,  it  gradually 
becomes  permanent.  The  characteristic  ova  are  found  very  early  in  the  urine. 
If  the  infected  individual  does  not  leave  the  country,  the  disturbance  is  aggra- 
vated by  affections  of  the  renal  pelvis  and  of  the  kidneys.  Stone-  in  the 
bladder  and  in  the  kidneys  develop  frequently.  We  have  mentioned  the 
tendency  t<>  the  formation  of  carcinoma.  Cole  Madden  describes  a  papilloma 
of  the  vagina  produced  by  the  ova  of  distoma.  The  mucous  membrane  of  the 
rectum  shows  similar  polypoid  excrescences  as  the  bladder.  The  nutrition 
becomes  defective  and.  finally,  after  a  course  Lasting  years,  death  occurs  with 
cachectic  manifestations.  It  Beems  tbat  severe  cases  are  most  frequenl  in 
Egypt.  In  South  Africa,  after  protracted  intermittent  attacks  of  hematuria 
and  cystitis,  the  disease  often,  at  least  apparently,  ends  in  recovery.  The 
destruction  of  the  parasite  doe-  not  in  it-elf  lead  to  recovery.  Sonsino  esti- 
mates the  duration  of  it-  life  at   two  to  three  years.      If  I  be  changes  have  been 

very  extensive,  the  morbid  symptoms  continue  to  develop  after  the  death  of 
the  parasite. 

34 


514  THE  ANIMAL  PARASITES  OF  MAN 

If  the  views  of  Loos  are  correct,  the  prophylactic  measures  are  plainly 
indicated.  In  the  infected  countries  energetic  measures  must  be  taken  to 
prevent  the  urine  of  infected  individuals  from  ever  reaching  the  rivers.  The 
embryos  will  soon  perish  in  closed  sewers.  The  greatest  precautions  are  neces- 
sary in  regard  to  bathing,  especially  in  the  neighborhood  of  habitations  in 
which  infected  persons  are  living. 

A  therapy  directed  to  the  expulsion  of  the  worms  will  probably  always 
remain  useless.  Efforts  to  expel  them  by  turpentine  oil  or  extractum  filicis 
maris  have  been,  according  to  the  reports  of  Brock,  unsuccessful.  We  are, 
therefore,  entirely  restricted  to  symptomatic  treatment. 

I  may  mention  another  trematode,  the 

Monostomum  lentis  of  Nordmann,  1832, 

which  was  once  found  in  an  extracted  lens;  this  form  is  probably  identical 
with  the  distomum  oculi,  Ammon,  1833. 

Hexathyridium  pinguicola,  Treutler,  1793,  and  hexathyridium  venarum 
are  also  counted  among  the  trematodes. 

CESTODES 

Cestodes,  tape-worms,  have  been  known  from  antiquity  as  parasites  of 
man.  Following  the  definition  of  Leuckart,  we  understand  by  cestodes  flat- 
worms  without  mouth  or  intestine,  which  develop  by  generation  and  by  gem- 
mation upon  a  scolex,  and  remain  united  for  some  length  of  time  in  a  ribbon- 
like colony. 

The  scolex,  known  under  the  name  "  head  of  the  tape-worm,"  is  supplied 
with  two  to  four  suctorial  discs,  and  generally  also  with  hooks  that  are  bent 
like  a  claw. 

The  head  serves  as  the  adhesion  apparatus.  The  flat,  two-edged  links  of 
the  chain  (proglottides)  grow  away  from  the  point  of  junction.  The  smallest 
links  contain  the  ova  in  which  develop  the  embryos  (oncospheres),  which  in 
the  bothriocephali  are  ciliated.  Only  these,  reaching  the  outside  world,  per- 
forate the  shell  of  the  ovum,  and  swarm  in  the  water  until  they  finally  reach 
an  intermediary  host.  The  ova  of  the  other  cestodes  emerge  into  the  outside 
world  with  the  feces,  or  still  enclosed  in  the  proglottid,  and  are  at  last  taken 
up  by  a  suitable  host.  The  oncospheres,  enclosed  in  small  cysts  or  embedded 
in  closed  cavities  of  the  body,  develop  in  the  host  into  scolices  which,  subse- 
quently, are  taken  up  by  the  actual  host  and  grow  into  tape-worms. 

The  best-known  of  the  tape-worms  parasitic  in  man  are  the  tenia  solium, 
Rudolph!,  1810,  and  the  tenia  saginata,  Goeze,  1782. 

I  may  forego  a  detailed  description  of  these  two  parasites,  since  they  are 
well  known.  I  shall  only  briefly  outline  their  differentio-diagnostic  charac- 
teristics. 

Tenia  solium  is  distinguished  by  a  head  which  is  supplied  with  a  rostellum, 
a  double  row  of  hooklets  and  four  suctorial  discs.  The  proglottides,  number- 
ing 800  to  900,  contain  the  testicles  and  the  easily  recognizable  uterus  con- 
sisting of  a  medial  trunk  and  of  seven  to  ten  lateral  branches  upon  either 
side.     The  marginal  sexual  papilla?  alternate  quite  regularly.     The  rounded 


CESTODES  515 

ova,  the  shells  of  which  are  radially  striated,  enclose  the  oncosphere  which  is 
supplied  with  six  hooklets. 

Malformations  arc  rarer  than  in  the  tenia  saginata.  I  wish  to  mention 
only  the  three-edged  or  prismatic  tenia  which  is  produced,  not  as  was  fre- 
quently assumed  from  a  twelve-hooked  oncosphere,  but  by  tin1  coalescence  of 
two  scolices  with  one-half  of  their  dorsal  surfaces,  whereas  the  other  two 
halves  remain  free;  it  appears  that  the  dorsal  parts  of  the  coalescent  halves 
are  at  the  same  time  greatly  retarded  in  growth. 

The  asexual  immature  form  is  the  Cysticercus  cellulosae,  the  firm  of  swine, 
which  is  found  principally  in  the  pig,  but  also  in  other  mammals.  The  mode 
of  infection  of  the  pig  and  of  man  is  well  known. 

The  Cysticercus  cellulosae  occasionally  also  -how-  malformations.  Such 
are  the  Cysticercus  (tenia)  acanthotrias  Weinland  and  the  Cysticercus  race- 
mosus  which  is  formed  like  a  hunch  of  grapes  and  possesses  many  branches; 
the  latter  is  found  in  the  brain  and  in  the  heart.  This  upsets  (according  to 
the  views  of  Redon,  Blanchard,  Raillet  and  Braun)  the  hypothesis  of  a  >pecial 
genus  of  tenia  (Cysticercus)  acanthotrias. 

The  second  variety,  the  tenia  saginata,  is  more  rounded  and  larger  than 
the  tenia  solium,  and  has  the  following  characteristics:  The  head  is  larger, 
the  row  of  hooklets  and  the  rostellum  are  ahsent  ;  the  suctorial  discs  are 
markedly   developed.      The  proglottides  are  supplied   with   irregularly  alter- 


Fig.  36. — Ova  of  Tenia  Solum.  Fig.  37. — Ova  of  Tenia  Saginata. 

The  enlargement  is  the  same  in  Fig.  36  and  Fig.  37. 

nating  sexual  papillae;  they  -how  a  uterus  with  20  to  30  ot  even  more  lateral 
branches;  the  Bexually  mature  members  which  are  cast  oil'  spontaneously  are 
frequently  found  without  ova,  because  the  latter  have  been  discharged  prema- 
turely owing  to  a  Lesion  of  the  uterus.  The  ova  are  similar  to  those  of  ihr  tenia 
solium  (see  Illustrations).  Malformations  in  the  chain  of  links  occur  more 
frequent ly  than  in  the  former  variety. 

Cysticercus  l><>\i-.  which  is  the  young  form  of  this  parasite,  is  principally 
found  in  cattle.  Whereas  the  Cysticercus  cellulosae  i-  Bometimes  found  in  the 
organs  of  man.  particularly  in  the  brain  and  in  the  eye.  generally  through 
autoinfection,  only  four  cases  have  been  reported  in  which  the  Cysticercus 
bovis  ha-  Keen  found  in  man.  It  i-  probable,  however,  that  these  four  i 
wer,,  not  dm-  to  the  Cysticercus  bovis  at  all.  but  to  malformations  of  the 
Cysticercus  cellulosae. 

Man   i-  considered   to  he  the  only  host  "I'  these  two  forms.     Deffke  suc- 
ceeded recently,  by  feeding  the  Cysticercus  cellulosae  to  ihr logs,  in  obtaining 

in  two  of  the  dogs  -mall  specimens  of  tenia  Bolium.  The  delicate  specimens 
gave  the  impression  that  they  were  in  the  process  of  expulsion. 

Tenia  solium  ha-  for  several  decades  become  steadily  rarer.    This  is  evi- 


516  THE  ANIMAL  PARASITES  OF  MAN 

dently  due  to  meat  inspection  during  which,  owing  to  its  size,  Cysticercus 
cellulosae  is  less  often  overlooked  than  Cysticercus  bovis. 

Tenia  cucumerina,  Bloch,  178G,  sive  elliptica  Batsch,  1782,  is  also  well 
known. 

This  tape-worm  is  frequently  found  in  large  numbers  in  the  dog  and  in 
the  cat.  The  small  rhomboid  head  shows  a  club-like  rostelluro  studded  with 
about  sixty  hooklets  arranged  in  four  rows.  The  cucumber-shaped  proglot- 
tides are  easily  detected  in  the  feces  of  the  dog. 

The  cysticercoid  young  form  inhabits,  according  to  Leuckart  and  Melni- 
koff,  the  abdominal  cavity  of  the  dog-louse,  of  the  dog-flea,  and,  more  rarely, 
of  the  human  flea.  The  habit  which  dogs  and  cats  have  of  swallowing  the 
parasites  that  infest  their  hairy  skins  sufficiently  explains  the  frequency  of 
the  infection.  This  tenia  occurs  rarely  in  man,  and  is  only  observed  in  small 
children.  Blanchard  reported  the  infection  of  an  adult  who  always  shared 
his  resting  place  during  the  night  with  his  dog. 

Quite  as  rare,  at  least  in  Germany,  is  the  following  tenia : 

Tenia  nana,  v.  Siebold,  1852. 

This  small  tenia,  only  2.5  cm.  long  and  0.5-0.7  mm.  broad,  is  characterized 
by  a  globular  head  supplied  with  a  rostellum  and  four  suctorial  discs.  The 
rostellum  is  covered  with  a  row  of  22-27  hooklets.  The  proglottides,  amount- 
ing to  about  200,  are  of  an  extended  oblong  form,  the  lower  20-60  of  a 
yellowish  color,  well-filled  with  ova.  The  sexual  papilla?  are  all  on  one  side. 
The  ova  are  covered  with  three  structureless,  transparent  shells  which  are  far 
apart  from  each  other. 

Nothing  is  as  yet  known  regarding  the  origin  and  development  of  this 
parasite. 

Leuckart  supposes  the  intermediate  hosts  to  be  insects.  According  to 
Grassi,  the  parasite  develops  without  an  intermediate  host,  as  does  the  tenia 
murina  (Dujardin),  which  by  many  was  formerly  considered  identical  with 
the  former.  The  anatomical  differences  between  these  tenia?  were  recently 
pointed  out  by  v.  Linstow. 

The  tenia?  live  in  the  small  intestine  in  colonies,  burrow  their  way  deeply 
into  the  mucous  membrane  of  the  gut,  and,  according  to  Grassi,  produce 
important  changes  in  it. 

The  parasite  has  been  observed  only  four  times  in  Germany,  and  in  all 
four  cases  Cologne  appeared  to  be  the  infected  locality.  It  may  possibly  often 
be  mistaken  for  the  oxyuris  vermicularis,  owing  to  their  similarity.  The 
parasite  has  been  observed  in  Egypt,  Eussia,  Servia,  Italy,  Japan  and  South 
America. 

Very  few  cases  of  the 

Tenia  flavopunctata,  Weinland,  1858, 

have  been  reported.  Its  identity  with  tenia  diminuta,  Rudolphi,  and  tenia 
leptocephala  Crepl.  is  established.  The  very  small  head  is  club-shaped,  with 
a  rudimentary  unprotected  rostellum.  The  proglottides,  2.5-3.5  mm.  broad, 
0.6-0.7  mm.  long,  present  in  their  center,  posteriorly,  a  yellow  area  which 


CESTODES 


oi; 


corresponds  to  the  male  sexual  organs.  The  intermediate  hosts  are,  according 
to  Grassi,  small  insects,  such  as  akis  spinoza,  anisolabis  annulipes,  asopia 
farinalis,  scaunis  striatus,  by  the  accidental  ingestion  of  which  man  may  also 
become  infected.  These  observations  were  confirmed  by  infection  experiments 
in  man  and  in  rats.  The  parasite  has  been  so  far  found  only  seven  times  in 
man,  and  almost  exclusively  in  children. 
Quite  as  rare  is  the 

Tenia  madagascariensis,  Davaine,  1869. 

This  tape-worm  is  about  25-30  cm.  long,  with  about  660-700  segments. 
The  head  is  supplied  with  four  large,  circular  suctorial  discs,  and  a  rostellum 
with  a  row  of  90  peculiarly  formed  hooklcts.  The  mature  proglottides  are 
2  mm.  long.  1.4  mm.  broad.  The  sexual  openings  are  situated  on  one  side. 
Each  proglottid  contains  120-150  small  round  ova.  We  are  ignorant  of  the 
exact  development"  of  the  parasite  and  only  know  thai  species  similar  to  this 
tenia  dwell  in  birds.  Only  five  cases  of  this  kind  have  been  observed  so  far 
in  the  tropics,  among  them  one  in  British  Guiana  (by  Daniels). 

It  appears  to  be  very  doubtful  whether  the  tenia  marginata.  Balsch,  1786, 
the  tenia  serrata,  Goeze,  17S?.  and  the  tenia  erassicollis  Rudolphi,  1810.  or 
their  evsticerces,  have  been  observed  in  man,  but  five  unknown  teniae  occurring 
in  man  have  been  reported,  and  have  been  called  the 

Tenia  confusa,  Ward,  1896. 

Ward,  in  a  preliminary  report,  has  described  a  tenia  found  in  man.  Its 
length  was  about  five  meters.  The  end  proglottides  measured  27-35  mm.,  the 
breadth  3.5-5  mm.  This  tenia  is  considerably  more  -lender  than  the  tenia 
saginata.  The  head  has  four  suctorial  discs,  and  a  retractile  rostellum  with 
six  or  seven  rows  of  small  hooks,  those  in  the  front  row  being  the  largest. 


Fig 


Figs.  88   12.     Tenia  confusa  Warb.    (After  Guyer.) 

38,  a,  o,  c,  d,  Chain  of  proglottides.     Fig.  39,  a  and  6,  Mature  proglottides.     I  ig    U),  I 
sexual  organs.     Fig    LI,  Male  sexual  organs.     Fig,  12,  Ovum  of  the  tenia  confusa. 


email 


The  proglottid-chain  is  distinguished  from  tenia  solium  and  tenia  Baginata 
by  continuous  longitudinal  musculature,  by  the  presence  of  a  tresicula  Beminalis 


518 


THE  ANIMAL  PARASITES  OF  MAN 


and  a  well-developed  receptaculum  seminis,  and  of  a  vaginal  sphincter.  The 
ovarian  tube  opens  into  the  lateral  wall  of  the  uterus.  Fourteen  to  eighteen 
lateral  branches  issue  from  each  side  of  the  uterus  but  are  not  perpendicular 
to  the  main  trunk.     The  yellowish  ova  are  of  ovoid  form. 

Tenia  africana,  v.  Linstow,  1900. 

The  German  colonial  possessions  have  given  us  the  knowledge  of  a  new 
tenia,  v.  Linstow  described  a  large  tenia  of  man  which  Dr.  Fülleborn  found 
in  a  negro  soldier  at  Lake  Nyassa.  The  scolex  is  unprotected,  and  is  smaller 
than  the  following  chain  of  segments.  The  proglottides,  even  the  terminal 
ones,  which,  besides  the  uterus  filled  with  ova,  contain  no  other  sexual  organs, 
are  broader  than  they  are  long.  The  uterus  consists  of  a  longitudinal  trunk 
extending  in  an  anteroposterior  direction  with  15-2-1  transverse  branches  on 
either  side  which  radiate  toward  the  center.  The  interior  organization  is 
different  from  that  of  tenia  saginata  in  all  essen- 
tial points.  The  suctorial  discs  are  enclosed  by 
rounded  projections  from  which  rays  extend  to  the 
periphery. 


a  b  c  d 

Fig.  43. — a-d,  Segment  chains  of  the  tenia  africana;  e,  scolex  from  the  vertical  plane;  /,  lumen 
of  a  suctorial  disc.     (After  v.  Linstow.) 


The  length  of  the  three  fragments  of  a  tenia  was  1,375  mm.;  whereas  the 
segments  of  the  tenia  africana  which  are  two  mm.  long  show  full  maturity; 
there  is  no  trace  of  sexual  organs  in  the  segments  of  the  tenia  saginata  which 
are  3.16  mm.  long  and  5.81  mm.  broad.  The  ova  are  ovoid,  0.012  mm.  long 
and  0.031  mm.  broad. 

Tenia  asiatica,  v.  Linstow,  1901. 

von  Linstow  recently  described  a  tenia  of  man  which  was  found  by  Anger 
in  Aschabad.  The  specimen  is  298  mm.  long;  the  segments  are  broader  than 
they  are  long  and  their  chain  is  narrow.  The  foremost  proglottides  have  a 
breadth  of  only  0.16  mm.  with  a  length  that  cannot  be  estimated.  Later  they 
increase  in  breadth  from  0.67-1.78,  and  in  length  gradually  to  0.99  mm.  The 
posterior  border  of  the  segments  slightly  overlaps  the  beginning  of  the  follow- 
ing one.  Seven  hundred  and  fifty  proglottides  were  present;  the  scolex  was 
absent.  The  formation  of  tbe  uterus,  as  well  as  that  of  the  otber  sexual 
organs,  suggests  that  this  variety  belongs  to  the  tenia  madagascariensis. 


CESTODES 


519 


Kecently,  in  the  Centralblatt  f.  Bad.  und  Parasit.,  1902,  Band  xxxi,  page 
770,  v.  Linstow  described  a 

Tenia  hominis  n.  spr. 

in  the  collection  of  helminthes  of  the  Musee  zoologique  de  l'Academie  Im- 
perial des  sciences  de  St.  Petersbourg.  This  tenia  was  found  by  Anger  in  a 
girl  in  Aschabad. 

The  scolex  was  2.01  mm.  long.  1.34  mm.  broad.     The  vertex  contained  a 
rudimentary  but  not  prominent  rostellum,  0.24  mm.  long,  entering  deeply 

into  the  scolex.  without  hooks. 
The  lumen  of  the  suctorial 
discs  extended  antero-posteri- 
orly,  so  that  they  formed 
regular  circles  upon  cross  sec- 
tions. A  ring-shaped  promi- 
nence was  noted  behind  the 
suctorial  discs. 


Fig.  44. — Tenia  asiatica.     (After  v.  T.instow.) 
4,  Tenia  asiatica,  natural  size;  H  and  C,  schematic  cross  sections:  />'.  with  male,  (\  with  female, 
sexual  organs;   g,  vessel;    n,  nerve;   //,  testicles;  va,  vas  deferens;  c,  cirrus  bag;  o,  ovary; 

d,  yolk  sac;  r,  receptaculum  seminis;   r,  vagina;  l>,  cross  section  through  a  segment   with 
masses  of  ova. 


The  chain  of  the  proglottides  was  In  nun.  long,  l.ll   mm.  broad  behind 
the  Bcolex,  1.91   nun.  posteriorly.     The  sexual  organs  were  not  developed. 

Hymenolepis  (drepanitotcenia)  lanceolata,  Bloch, 
a  parasite  found  in  many  water-fowl,  was  re- 
cently expelled  in  two  specimens  by  a  boy  twelve 
years  old.  The  scolex  was  noi  found.  The 
Length  of  the  tenia  is  85  99  mm.,  it-  greatesl 
breadth  behind  the  center  of  the  body  length  is 
8.6  12  nun.  The  proglottides  are  all  consider- 
ably broader  than  long.  The  leaf-like  thin  stro- 
bile   slightly    tapers    toward    the   anterior   end; 

posteriorly  it  extend-  in  uniform  breadth  and   its 

termination  is  rounded.  The  ova  possess  the 
shells  which  are  characteristic  of  the  genua  hy- 
menolepis, being  far  apart    from  each  other. 

This    parasite    uses,    as    intermediate   hosts,    ,  „.   ,-     (-11:,,„^1  raoM  ,■„._ 

fre8h  water  crabs  ;  the  cercocysts  are   found  espe-        an -  [NcoNGBr/BNS,   L900. 


520 


THE  ANIMAL  PARASITES  OF  MAN 


cially  in  the  cyclops  serrulatus,  Fischer,  and  diaptorrms  spinosus,  Daday;  and 
since  these  are  frequently  found  in  stagnant  waters,  the  occurrence  of  the 

parasite  in  geese  and  ducks  is  quite 
natural.  The  crabs,  which  are  often 
difficult  to  recognize,  occasionally  mi- 
grate with  the  drinking-water  into  the 
intestinal  canal  of  man;  the  cercocyst 
inhabiting  the  crabs  develops  into  hy- 
menolepis  lanceolata. 


Fig.  46.  —  Hymeno- 
lepis  Lanceolata, 
Bloch.  Enlarged 
about  t  wenty  times . 


Fig.  47.  —  Head, 
Greatly  En- 
larged. 


Fig.  48. — Proglottid  of  Hymenolepis. 
This  preparation  I  owe  to  the  kindness  of  Pro- 
fessor W.  Müller  of  Greifswald. 


The  most  familiar  of  the  bothriocephali  is  the 

Bothrlocephalus  latus,  Bremser,  1819. 

This  broad  bothriocephalic,  called  also  the  pit-head,  measures  5-9  meters 
and  is  the  longest  tape-worm  of  man.  The  club-shaped  head  shows  on  its 
lateral  border  on  each  side  an  elongated,  slit-like  pit.  The  individual  pro- 
glottides, 3,000  to  4,200  in  number,  are  remarkably  broad  in  proportion  to 
their  length.  A  grayish-blue  centerpiece  of  rosette-like  form  bordered  by 
two  narrower  bands  is  distinctly  visible  upon  both  surfaces.  On  the  ventral 
surface  are  the  male  sexual  opening  and  the  mouth  of  the  vagina.  The 
mature  ova  are  ovoid  in  form  and  surrounded  by  a  brownish  shell  with  a  lid. 
The  ova  are  rarely  found  in  the  last  mature  segments  of  the  chain.  Large 
numbers  of  proglottides  are  often  expelled  at  once.  They  are  voided  with  the 
feces,  having  been  previously  discharged  from  the  uterus.  If  the  ova  reach 
the  water,  ciliated  embryos  develop  within  them,  which  slip  from  the  shell 
of  the  ova  and  float  for  some  time  in  the  water.  The  ciliated  covering  perhaps 
seeks  the  intermediary  host,  which,  as  we  learn  from  Braun's  brilliant  investi- 
gations, was  found  to  be  the  pike  (esox  lucius),  the  burbot  (lota  vulgaris), 
the  perch  (perca  fluviatilis),  the  trutta  vulgaris  and  lacustris,  the  thymallus 
vulgaris,  and  the  onchorhynchus  Perryi.  It  is  still  undecided  whether  this 
list  exhausts  the  number  of  intermediate  hosts. 

The  young  of  the  bothriocephalus,  plerocercoides,  dwell  encapsulated  in 
various  parts  of  the  intestines  and  of  the  musculature,  and  usually  in  large 
numbers. 

Bothriocephali  have  been  cultivated  by  feeding  experiments  with  plero- 
cercoides in  the  dog,  the  cat,  and  also  in  man. 

The  transmission  of  the  parasite  undoubtedly  occurs  by  means  of  fish.  It 
takes  place  frequently  in  infected  districts  where  fish  are  eaten  raw,  half 
cooked,  or  after  any  other  mode  of  preparation  which  does  not  effect  a  destruc- 
tion of  the  ova.  It  is  remarkable  that  living  ova  have  been  demonstrated 
even  in  fish  that  were  frozen  stiff. 


CESTODES  521 

The  geographical  distribution  of  the  bothriocephalic  is  a  limited  one.  It 
has  been  frequently  noted  in  the  Russian  Baltic  provinces,  in  the  northeastern 
part  of  Sweden,  in  Denmark,  East  Prussia,  Russia  and  Poland.  Its  presence 
has  also  been  determined  in  the  coast  districts  of  Belgium,  Holland,  northern 
France,  and  in  Ireland.  It  is  remarkably  common  in  the  western  parts  of 
Switzerland,  on  the  shores  of  Lake  Geneva  and  Lake  Neufchätel,  and  in  those 
parts  of  France  and  Italy  bordering  upon  Switzerland.  The  parasite  is  often 
seen  in  Japan.  It  is  found  sporadically  in  Germany,  in  Rhenish  Hesse,  Berlin, 
Nuremberg,  Munich  and  Greifswald,  and  has  been  found  in  North  America. 

Of  the  other  bothriocephali  we  find  in  man  the 

Bothriocephalus  cordatus,  Leuckart,  1862. 

This  variety  is  characterized  by  a  short,  broad,  heart-shaped  head  which  is 
supplied  with  two  suctorial  disc-like  pits.  The  parasite  which  is  chiefly  found 
in  various  mammals  in  Greenland  and  in  Iceland  is  occasionally  also  noted 
in  man. 

The  tape-worm  described  as 

Bothriocephalus  cristatus,  Davaine,  1874, 

may  possibly  represenl   only  another  form  of  the  bothriocephalus  latus.     Its 
head  is  characterized  by  two  extremely  long,  helmet-like  points. 
Of  another  variety  of  bothriocephalus, 

Bothriocephalus  Mansoni,  Cohbold,  1883, 

only  plerocercoides  have  as  yet  1 n  observed,  and  these  apparently  wander  in 

the  body  of  man.    Tiny  finally  reach  the  skin,  and  there  cause  abscess  forma- 
tions, or  they  enter  the  urinary  passages  whence  they  are  discharged  with  the 

urine. 

Bothriocephalus  grandis,  Blanchard,    1894. 

Tjima  and  Kurimoto  have  observed  a  bothriocephalus  previously  unknown, 
which  lack.-  a  head  portion.    It  measures  in  breadth,  anteriorly.  1.5  mm.,  pos- 


'  ■■:< 
I'm.   49.—  BOTHBIOCl  PHAL1  B  QraNDIB.      PROGLOTTID   INdOti  m.      (After  Ijima  and  Kurimoto.) 

toriorly,  25  mm.    The  proglottides  are  extremely  -hurt,  and  arc  supplied  with 
a  double  genital  apparatus. 

The  ventral  BUrface  contain-  the  genital  pori,  anteriorly  the  mouth  of  the 

cirrus  and  that  of  the  vagina,  behind  the-e  that  ..I'  the  uicrii-.     The  ova  pOfi 

a  lid.  arc  thick-shelled  and  brown;  their  length  is  <u»<;:;  nun.,  their  breadth, 
0.048  mm.    They  contain  a  mulberry-like  ma--  of  Hue  globules. 

There  can  be  no  doubt   that   parasites  infecl   some  persons  in  whom   no 
deleterious  influence  upon  the  health  i-  manifest.    The  patients  in  Buch  cases 


522  THE  ANIMAL  PARASITES  OF  MAN 

are  often  unaware  of  the  presence  of  their  guest  until  they  note  the  discharge 
of  proglottides.  The  distressing  thought  of  being  the  host  of  such  a  guest 
causes  the  carriers  of  the  parasite  to  seek  medical  aid.  Strong,  robust  persons, 
owing  to  their  good  constitution,  are  often  uninjured  by  the  parasite.  A  weak 
constitution  and  sensibility,  or  other  factors  which  are  especially  the  cause  of 
disintegration  of  the  blood  leading  to  pernicious  anemia,  will  produce  symp- 
toms in  the  affected  individuals,  sometimes  even  the  most  severe  morbid 
phenomena. 

There  are  patients  who  harbor  the  parasite  for  years  without  presenting 
the  slightest  sign  of  helminthiasis.  On  the  other  hand,  in  sensitive  persons 
the  symptoms  may  be  numerous.  In  all  cases  the  most  positive  indication  is 
the  passage  of  segments  of  the  worm,  which  occurs  at  times  spontaneously, 
at  other  times  with  the  feces.  With  tenia  saginata  the  spontaneous  discharge 
of  proglottides  appears  to  be  more  frequent  than  with  tenia  solium.  In  the 
case  of  the  bothriocephalus  segments  in  chains  amounting  to  several  meters  in 
length  are  passed. 

Not  infrequently  the  ingestion  of  very  salty  food,  of  blueberries,  straw- 
berries, salad,  or  of.  alcoholic  drinks,  causes  the  passage  of  segments.  In  very 
rare  cases,  proglottides  are  vomited.  By  reason  of  abnormal  protrusion  of  the 
intestines  or  of  the  pelvic  organs  from  the  abdominal  coverings,  proglottides 
occasionally  appear  externally. 

Besides  these  symptoms  the  microscopic  examination  of  the  feces  is  of 
especial  importance  in  the  diagnosis.  This  should  never  be  neglected  if  the 
presence  of  tape- worm  is  suspected.  Very  frequently  by  careful,  oft  repeated 
examinations  of  fecal  masses  indistinct  symptoms  on  the  part  of  the  digestive 
apparatus,  of  the  nervous  system,  or  of  the  general  nutrition,  have  been  ex- 
plained, and  treatment  directed  into  the  proper  channels.  As  the  uterus  of 
the  tenia  has  no  exit,  the  eggs  can  only  find  egress  when  the  uterus  of  the 
mature  proglottid  is  injured.  In  the  case  of  tenia  saginata,  discharge  of 
the  eggs  is  almost  the  rule.  The  proglottides  which  are  discharged  are  usually 
without  eggs.  The  ova  of  the  bothriocephalus  are  extruded  into  the  feces  from 
the  uterus  which  has  an  external  mouth.  These  may  readily  be  differentiated 
from  the  eggs  of  teniae,  whereas  the  eggs  of  tenia  saginata  and  tenia  solium 
only  differ  by  their  variation  in  size. 

Besides  the  ova,  Charcot-Bobin's  crystals  are  found  in  the  feces  as  in  the 
case  of  other  helminthiases. 

Whereas  the  passage  of  ova  and  proglottides  is  the  most  positive,  and 
occasionally  the  only,  symptom  of  an  existing  tape-worm,  the  other  symptoms 
of  tenia  permit  us  to  recognize  the  presence  of  a  tape-worm  with  but  slight 
probability,  in  some  patients  there  are  disturbances  of  the  digestive  apparatus. 
I  shall  only  mention  here  pyrosis,  bulimia,  nausea,  a  longing  for  spicy  food, 
etc..  symptoms  which,  as  is  well  known,  are  grossly  exaggerated  in  the  pam- 
phlets of  quacks  to  attract  the  attention  of  patients.  In  others  there  are 
colicky  pains  which  are  occasionally  more  severe  after  taking  sour  food,  and 
better  after  fluids.  It  is  evident  that  the  tape-worm  acts  as  a  foreign  body 
in  the  intestinal  canal,  and  may  exert  a  powerful  irritation  in  the  region  it 
inhabits.     Probably  the  booklets  which  some  teniae  possess  may  share  in  this 


CESTODES  523 

irritant  action.  If  the  tape-worm  is  only  seen  after  it  has  been  expelled,  or 
after  it  has  died,  it  is  difficult  to  understand  what  energy  and  motility  the 
parasite  possesses  under  normal  circumstances  in  the  warm  intestine  of  its 
host,  and  how  greatly  it  may  irritate  the  intestinal  mucous  membrane.  This 
may  be  noted  sometimes  as  pain,  at  other  times  as  a  digestive  disturbance. 
Intestinal  catarrh,  constipation,  marked  irregularity  of  the  bowels  are,  in 
fact,  very  frequent  accompaniments  of  tape-worm  disease.  We  have  repeat- 
edly noted  the  disappearance  of  all  these  symptoms  after  the  removal  of  the 
parasite. 

Besides  these  local  symptoms,  in  a  number  of  patients  suffering  from 
tape-worm  there  are  also  general  phenomena  and  so-called  reflex  symptoms, 
existing  alone  or  together  with  the  gastric  phenomena.  It  is  quite  certain 
that  formerly  in  investigating  these  symptoms,  as  the  result  of  incorrect  views 
and  on  account  of  erroneous  pathological  deductions,  diagnoses  have  been 
made  which  would  not  bear  strict  critical  analysis.  To  deny  them  utterly 
would,  however,  not  be  correct.  There  are  to  be  mentioned :  Vertigo,  and 
attacks  of  syncope,  headache,  stubborn  singultus,  pupillary  differences,  rapid 
change  of  color  in  the  face,  pruritus,  spasmodic  attacks  which  occasionally 
have  the  characteristics  of  epilepsy.  According  to  the  observations  of  Grassi, 
in  the  case  of  tenia  nana  epileptic  attacks  are  especially  frequent.  In  deciding 
upon  the  connection  of  phenomena  of  this  kind,  it  will  aid  us  in  every  case 
to  note  whether  they  persist  after  the  disappearance  of  the  worm,  and  are 
therefore  to  be  looked  upon  as  a  purely  reflex  condition.  If  this  be  the  case 
they  are,  of  course,  only  an  accidental  complication. 

How  far  the  symptoms  on  the  part  of  the  nervous  system  are  to  be  regarded 
as  reflex,  cannot  always  be  immediately  decided.  We  must  lir-t  exclude  those 
cases  in  which  Cysticercus  invasion  has  to  be  considered,  as  in  the  case  of  tenia 
solium.  We  know  positively  from  autopsies  that  the  brain  is  the  seal  by  pref- 
erence of  cysticerci.  On  the  contrary,  it  must  be  questioned  whether  the 
central  nervous  organs  are  not  under  the  influence  of  toxic  substances  produced 
by  the  parasite.  It  is  more  than  likely  that  these  animal  parasites  engender 
toxic  products  which  have  a  particularly  deleterious  effect  upon  the  nervous 
Bystem  as  well   a-   upon   blood   format  ion. 

Beyher,  Runeberg,  Schapiro,  Dehio  and  others  have  called  attention  to  the 
fact  lhat  the  severe  anemic  conditions  occurring  in  persons  affected  with 
the  bothriocephalic  may  assume  the  character  of  pernicious  anemia  and  run 
a  course  a-  such.  These  Bymptoms  may  certainly  be  referred  to  the  presence 
of  the  parasite.  There  is  no  Longer  any  doubt  of  the  etiologic  connection. 
The  circumstance  thai  the  majority  of  infected  persons  are  not  anemic  sug- 
gests the  though!  that  the  poison  is  found  only  umler  special  circumstances 

a-,  for  instance,  tin'  illness  or  death  of  the  worm,  or  the  presence  of  the  para- 
site for  a  considerable  time.  Lately  Schaumanrj  ami  Talqvisl  led  dogs  with 
segments  of  the  bothriocephalus  taken  from  a  case  of  pernicious  anemia,  and 
produced  undoubted  dissolution  of  blood  in  the  dog.  The  forms  of  bothrio- 
cephalus which  do  no!   produce  anemia  also  contain  the  hematogenous  poison. 

Occasionally  this  i>  present  in  other  tenia'.     Bisenlohr  soon  effected  a  cure  of 

a  case  of  severe  anemia  by  expulsion  of  a  tenia  saginata, 


524  THE  ANIMAL  PARASITES  OF  MAN 

In  conclusion  I  must  mention  the  fact  that  persons  who  have  previously 
been  the  hosts  of  parasites,  and  even  persons  who  have  never  been  affected 
by  tape-worm,  but  who  have  read  or  heard  of  the  symptoms  of  helminthiasis, 
occasionally  suffer  from  hypochondria  verminosa  or  teniaphobia.  Nervous 
disturbances  which  appear  incidentally  are  referred  to  the  presence  of  a  tape- 
worm. That  hysterical  or  hypochondriacal  individuals  are  particularly  pre- 
disposed to  these  conditions  is  so  obvious  that  it  need  not  be  especially  dwelt 
upon. 

On  account  of  the  great  number  of  local  and  general  symptoms  caused  by 
the  presence  of  this  parasite,  considerable  experience  must  have  been  acquired 
to  make  one  suspect  the  presence  of  a  tape-worm.  Certain  symptoms  which 
are  occasionally  present  in  helminthiasis  arouse  this  suspicion.  Among  these 
are  the  complaints  that  the  symptoms  are  most  distressing  when  the  stomach 
is  empty,  and  that  the  disturbances  are  less  on  taking  sweet  food,  but  are 
increased  by  salty  or  acid  food.  However,  I  never  begin  a  tape- worm  treat- 
ment until  after  the  presence  of  the  parasite  has  been  proven  by  the  passage 
of  proglottides  or  the  eggs  in  the  feces.  In  examining  these  the  physician 
must  be  careful  not  to  confound  remnants  of  undigested  food,  mucus  casts, 
and  shreds  of  tendons,  often  mistaken  by  the  laity  for  proglottides,  and  thus 
make  an  erroneous  diagnosis.  Dry  proglottides  after  being  soaked  in  water 
soon  assume  their  characteristic  form.  As  a  rule,  the  microscopic  determina- 
tion of  the  eggs  of  the  tenia  enable  us  to  make  the  diagnosis  earlier  and 
with  greater  certainty  than  by  the  macroscopic  proglottides.  The  encapsulated 
eggs  of  the  bothriocephalus  are  readily  recognized,  but,  as  has  already  been 
mentioned,  the  differentiation  between  the  eggs  of  tenia  solium  and  tenia 
saginata  is  more  difficult. 

To  recognize  from  the  shape  of  the  proglottid  which  variety  is  present 
it  is  advisable  to  fix  this  between  two  glass  slides.  The  proglottid  of  the 
tenia  solium  is  more  delicate  and  more  transparent  than  the  tougher  segments 
of  the  tenia  saginata.  In  the  former  the  structure  of  the  branching  uterus 
is  more  plump,  the  number  of  lateral  twigs  only  amounts  to  from  7  to  10, 
while  the  uterus  of  the  tenia  saginata  shows  from  20  to  50  and  more  lateral 
twigs.  For  the  recognition  of  the  less  frequent  parasites  special  text-books 
on  the  subject  must  be  consulted. 

PROGNOSIS 

The  prognosis  is  generally  favorable.  Even  in  cases  of  severe  bothrioceph- 
alus anemia  cure  has  generally  taken  place  after  the  removal  of  the  parasite. 
Parasitism  with  the  tenia  solium  necessitates  special  care  on  account  of  the 
danger  of  autoinfection  with  the  hooklets.  It  is  particularly  apt  to  occur 
from  the  appearance  of  ripe  proglottides  in  the  stomach  as  the  result  of  anti- 
peristaltic movements.  Prolonged  presence  of  the  proglottides  in  the  stomach 
explains  why,  in  some  persons,  the  Cysticercus  is  found  with  such  extraordi- 
nary frequency  in  the  brain  and  in  the  musculature.  Even  in  the  eye  occa- 
sionally more  than  one  Cysticercus  is  found.  The  host  of  the  tenia  solium 
is  also  a  certain  menace  to  those  about  him.  By  insufficient  cleanliness, 
by  careless  handling  of  the  proglottides   which   have  been  passed,  and   by 


CESTODES  525 

contact  with  fecal  masses,  the  possessor  of  a  tenia  solium  may  spread  the 
infection. 

THERAPY 

Prophylactic  measures  are  based  on  the  history  of  the  development  of  these 
parasites.  In  the  first  place  the  spread  of  Cysticercus  disease  among  animals 
used  for  food  must  be  prevented,  and  not  only  the  tape-worms  which  are 
voided,  but  also  the  feces  of  the  patient  with  tape-worm  disease  should  be 
effectually  destroyed,  best  by  fire.  All  who  harbor  the  parasites  should  be 
placed  under  treatment  as  soon  as  possible,  particularly  such  persons  as  come 
in  contact  with  animals  used  for  food.  The  patients  must  be  instructed 
never  to  defecate  in  the  open  air. 

The  dissemination  of  tape-worm  is  actively  combated  by  the  erection  of 
abattoirs  and  the  introduction  of  compulsory  meat  inspection.  It  is  true  this 
protection  is  not  absolute,  for  even  with  experienced  meat  inspectors  some 
cysticerci  which  are  deeply  hidden  in  the  muscles  may  be  overlooked.  I  refer 
particularly  to  the  small  cysticerci  which  are  few  in  number,  as  in  the  case 
of  the  tenia  saginata.  Cleanliness  in  the  kitchen  and  in  the  household,  espe- 
cially in  handling  raw  meat,  is  absolutely  necessary.  Vessels  in  which  raw 
unat  is  kept  should  not  be  used  for  other  food  substance-.  Thorough  boiling 
kills  the  Cysticercus  as  well  as  corning,  with  or  without  subsequent  smoking. 
The  process  of  smoking,  alone,  by  no  means  prevents  the  development  of  the 
cysticerci.  The  heat  in  the  inner  parts  of  the  meat  to  be  smoked  certainly 
does  not  reach  50°  C.  and  an  absolute  protection  is  therefore  not  obtained. 

The  removal  of  the  tape-worm  in  delicate  children,  in  the  aged,  during  the 
course  of  acute  diseases,  particularly  severe  intestinal  diseases,  and  during 
menstruation  and  pregnancy,  is  usually  contraindicated. 

I  carry  out  the  treatment  in  the  course  of  a  day  in  which  I  may  personally 
superintend  it.  For  a  long  time  the  actual  treatment  is  preceded  by  a  prepara- 
tory one.  1  have  been  unable  to  convince  myself  of  the  value  of  a  prolonged 
preparation.  On  the  day  before  the  treatment  is  begun,  I  give  milk,  and 
prohibit  food  containing  sugar,  so  that  the  worm  will  have  no  favorable  nutri- 
tive material.  After  the  midday  meal,  if  at  all  possible,  I  give  only  coffee; 
in  the  evening,  bouillon,  eggs,  a  little  wheat  bread,  perhaps  some  red  wine 

diluted    with    water.      At   night  the   patient    is  given   a   tablespoonful    of  castor 
oil  or  an  enema. 

Among  numerous  vermifuges,  which  I  do  not  intend  to  enumerate  here. 
1  prefer  radix  filices  or  the  ethereal  extract  of  male  fern,  and  order  extr. 
lil.  mar.  Beth.  5.0  6.0  7.5  Hi. ii.  Byr.  simpl.  tO.O,  M.D.S.,  to  be  taken  within 
ten  minute-.  Children  receive  a  correspondingly  smaller  dose.  The  tape-worm 
is  to  lie  stupefied  by  the  remedy,  and  to  be  subsequently  exposed  to  it-  action. 
If  nausea  or  vomiting  occur.  I  give  -mall  pellets  of  ice,  some  brandy,  or  a 
little  lemonade.  I  am  also  quite  fond  of  employing  Helfenberg's  Tape-worm 
Remedy,  which  consists  in  the  administration  of  eighl  capsules  that  contain 

one  gram   of   fil.   mar.   and    2   irnmi-  of  castOT  oil.      According   to   the   patient. 
I  Lri\e  6  or  s  capsules  at  once,  and.  after  an  hour,  T  cap-tile-  which  contain  the 

castor  oil.     I  will  briefly  describe  my  method  of  treatment. 


526  THE  ANIMAL  PARASITES   OF  MAN 

The  patient  is  required  to  go  to  bed.  A  bed-pan,  irrigator,  lukewarm 
water  and  a  black  pus  basin  are  to  be  ready  at  band.  The  remedy  must  be 
given  in  the  morning  before  food  is  taken.  To  prevent  nausea  and  vomiting, 
small  pellets  of  ice,  brandy,  or  lemonade  are  taken.  After  an  hour,  one  or 
two  tablespoonfuls  of  castor  oil  are  administered.  If,  after  one  or  two  hours* 
the  worm  has  not  been  passed,  an  attempt  should  be  made  by  the  injection  of 
a  large  amount  of  lukewarm  water  into  the  rectum,  to  expel  the  parasite,  which, 
very  frequently,  has  only  been  stunned.  These  injections  are  absolutely  neces- 
sary if  large  portions  of  the  parasite  are  passed,  as  they  readily  break  upon 
manual  extraction.  If  the  head  of  the  worm  remain  in  the  intestine,  an 
attempt  must  be  made  to  expel  this  by  the  injection  of  a  larger  amount  of 
water. 

This  treatment  may  be  regarded  as  successful  when  the  head,  or,  more  cor- 
rectly, the  heads,  have  been  found.  The  search  for  the  head,  which  is  often 
detached,  is  facilitated  by  placing  the  worm  which  has  been  passed  in  the  flat 
black  basin.  In  spite  of  the  greatest  vigilance,  it  is  occasionally  impossible  to 
find  the  head.  The  result  of  the  treatment  is  then  questionable.  It  should, 
however,  only  be  repeated  if,  after  eight  to  ten  weeks,  new  proglottides  are 
passed,  showing  that  the  previous  treatment  has  been  unsuccessful. 

ECHINOCOCCUS   DISEASE 

Echinococcus  disease  in  the  human  subject  is  of  increasing  importance, 
many  cases  having  come  under  observation.  I  shall  here  consider  the  subject 
as  briefly  as  is  consistent  with  accuracy. 

The  echinococcus  polymorphus  is  the  encysted  Cysticercus  of  the  tenia 
echinococcus  discovered  by  v.  Siebold  in  1853,  and  is  found  chiefly  in  the 
small  intestine  of  the  dog,  the  jackal  and  the  wolf.  The  assumption  that  the 
fox  also  may  be  a  carrier  and  distributer  of  the  tenia  echinococcus  has  not  vet 
been  proven. 

The  tape-worm  has  a  length  of  from  4  to  5  mm.  The  head  is  armed  with 
a  rostellum  and  a  double  row  of  hooklets.  The  number  of  joints  is  only  three ; 
immediately  after  the  last  joint  is  desquamated  a  new  portion  forms.  The 
last  joint,  which  contains  the  mature  eggs,  comprises  almost  two-thirds  of  the 
entire  length  of  the  worm;  it  is  of  extremely  delicate  texture,  and  is  easily 
lacerated. 

If  parts  of  the  infective  proglottides  reach  the  stomach  of  man  and  of  cer- 
tain animals,  the  tissue  of  these  undergoes  digestion  by  the  gastric  juice,  but 
the  eggs  which  have  been  set  free  are  not  digested,  nor  is  the  embryo.  This 
has  six  hooklets  which,  emerging  from  the  egg,  penetrate  the  intestinal  wall, 
and  thence  in  a  more  or  less  direct  way  reach  the  point  where  they  later  develop. 
It  is  quite  probable  that  many  of  the  eggs  and  embryos  perish  on  account  of 
the  digestive  power  of  the  gastric  juice,  and  are  eliminated  with  the  fecal 
masses,  for,  otherwise,  multiple  echinococci  would  not  be  so  exceedingly  rare 
— much  rarer  than  the  solitary  form.  According  to  van  Beneden  and  Leuck- 
art,  the  embryos  forcibly  penetrate  the  walls  of  the  intestine,  and  finally  reach 
the  blood  and  lymph-vessels,  in  which  they  are  carried  onward.     The  fact  that 


ECHINOCOCCUS   DISEASE 


527 


they  breed  in  the  capillaries  of  the  portal  circulation  explains  the  frequent 
implication  of  the  liver.  Often  the  embryos  lodge  permanently  in  the  mesen- 
teric glands.  Others,  by  means  of  the  lymph-vessels,  or  by  various  avenues 
of  communication,  invade  the  peritoneal  and  pleural  cavities:  others  enter  the 
thoracic  duct,  thence  find  their  way  into  the  jugular  vein  and  to  the  right 
heart,  and  are  retained  in  the  lung  or  are  distributed  to  near  or  even  distant 
organs. 

After  the  echinococcus  embryo  has  reached  its  destination  it  develops  very 
slowly;  we  would  digress  too  far  if  we  described  the  individual  phases  of  its 
development. 

After  the  lapse  of  weeks  or  months,  we  again  find  the  echinococcus  in  a 
round  white  cyst  which  gradually  increases  in  size.  Its  walls  are  composed 
of  a  characteristically  layered  cuticula  and  a  parenchymatous  Layer.  After  a 
certain  time  the  latter  shows  upon  its  inner  surface  the  so-called  breeding 
capsules,  which  hang  upon  a  short  pedicle  from  the  parenchymatous  layer,  and 
are  surrounded  by  a  transparent  fluid  not  containing  albumin.  Some  of  the 
breeding  capsule-  develop  internally,  some  externally, 
producing  echinococcus  heads,  the  so-called  scolices. 


Fio.  50. — Tenia  I  '■>  hin'ococctjs. 
Greatly  enlarged. 


Fig.  51. — Head  of  the  Echinoi  occtts: 
a,  with  projected,  and  /;,  with  retracted,  head. 


In  many  cases  daughter-cysts  are  formed.  These  originate  from  embryos 
which  probably  represenl  original  parts  of  the  parenchymatous  layer,  bin  have 
remained  intralamellar.  They  Lead  to  cysl  formation  surrounded  by  its  own 
cuticula.  Gradually  bulging  inward,  they  finally  reach  the  cysl  cavity.  We 
then  speak  of  echinococcus  bydatidosus  or  endogenus.  This  endogenous 
daughter-cysl  development  is  opposed  by  the  exogenous,  which  occurs  mostly 
among  our  animals  used  for  food,  Imi  may  even  occur  in  man.  The  daughter- 
cysts  may  later  form  other  cysts.  The  contents  of  the  cysi  are  colorless  and 
clear,  or  slightly  opalescent.  The  fluid  contain-  albumins  which  are  not  pre- 
cipitated by  boiling,  also  common  salt,  succinic  acid  and  sugar;  occasionally 
inosite,  Leucin  and  tyrosin. 

The  echinococcus  cysl  at  any  stage  of  it-  developmenl  may  become  Bterile; 
i.e.,  the  formation  of  scolices  (acephalocysts)  ceases.  Not  rarely  the  echino- 
coccus worm  becomes  diseased  and  dies.  The  fluid  becomes  turbid,  the  walls 
of  the  cysl  collapse,  the  parenchymatous  Layer  softens  and  fatty  degeneration 


528  THE  ANIMAL  PARASITES  OF  MAN 

takes  place.  The  head  falls  off,  is  partly  destroyed  or  undergoes  more  or  less 
change,  and  swims  about  in  the  fluid.  The  contents  thicken.  A  considerable 
deposit  of  calcium  salts  occurs  and  the  shrunken  sac  may  finally  be  represented 
by  a  single  calcified  nodule. 

The  echinococcus  multilocularis,  which  in  form  so  strongly  resembles  an 
alveolar  colloid  of  the  liver  that  hitherto  its  original  nature  has  often  been 
entirely  misunderstood,  must  next  be  mentioned.  It  is  found  chiefly  in  the 
liver,  but  also  occasionally  in  the  brain,  the  heart,  the  diaphragm,  and  the 
pleural  cavity ;  in  the  psoas  muscle,  the  lung,  the  gall-bladder,  the  kidney,  and 
the  adrenals ;  in  the  uterus  and  anterior  wall  of  the  chest ;  in  the  duodenum ; 
in  the  portal  and  peribronchial  lymph-glands  and  in  the  bones.  The  multi- 
locular  or  alveolar  echinococcus  is  characterized  by  small  irregularly  formed 
cysts  which  are  separated  from  one  another  by  masses  of  connective  tissue 
enclosing  a  gelatinous  plug.  In  section  we  recognize  a  honeycomb-like  struc- 
ture. All  the  cysts  possess  the  properties  of  echinococcus  cysts  except  for  slight 
deviations.  Upon  the  inner  surface  there  are  frequently  layers  of  granular 
fatty  material  or  pigment,  besides  balls  with  radiating  stripes  which  consist  of 
an  organic  base  impregnated  with  calcium  salts.  Not  rarely  needle-shaped 
or  sheaf-like  crystals  and  hematoidin  crystals  are  also  noted.  Scolices  are 
often  absent. 

The  limits  of  the  tumor  are  quite  sharply  circumscribed.  Now  and  then 
smaller  isolated  tumors  are  found  adjacent.  Virchow  saw  strands  resembling 
a  pearl  necklace,  the  parts  of  which  projected  like  processes.  The  capsule  is 
invariably  of  a  cartilaginous  hardness,  and  adherent  to  the  surrounding  tissues. 

This  echinococcus  was  for  a  long  time  held  to  be  only  a  variation  in  the 
form  of  the  cystoid  echinococcus,  due  to  its  growth  in  the  blood-vessels,  lymph- 
vessels,  and  biliary  channels. 

Its  characteristic  alveolar  structure,  as  well  as  the  conspicuous  variation  in 
its  geographic  distribution,  has  raised  doubts  as  to  the  identity  of  the  multi- 
locular  with  the  hydatid  forms.  To  decide  this  question,  experiments  in 
feeding  dogs  with  the  echinococcus  multilocularis  were  undertaken.  Klemm, 
Vogler,  Mangold,  and  Müller  raised  teniae  which  in  the  form  of  their  hook- 
lets,  as  well  as  in  the  position  of  the  eggs  in  the  terminal  section,  differed 
from  the  tenia  of  the  cystoid  form.  Mangold  also  succeeded,  by  feeding  with 
a  tenia  which  he  had  raised,  in  developing  two  tumor  foci  in  the  liver  of  a  pig; 
these  were  recognized  as  echinococcus  multilocularis.  The  occurrence  of  mul- 
tilocular  echinococcus  in  certain  geographical  regions  is  well  known.  Accord- 
ing to  Vierordt,  it  is  found  frequently  in  Württemberg,  Switzerland,  Bavaria, 
also  in  Austria  and  Russia,  occasionally  in  Prussia,  Baden  and  North  America. 
Recently  Posselt  has  called  attention  to  a  previously  unknown  region  of  dis- 
tribution in  the  Tyrol;  Pichler  described  a  case  of  echinococcus  multilocularis 
in  Kärnten.  It  is  especially  interesting  to  note  that  in  the  "  classical  coun- 
tries "  of  the  hydatid  echinococcus,  Iceland,  Australia,  Mecklenburg  and  New 
Pomerania,  Dalmatia  and  Argentina,  the  echinococcus  multilocularis  does  not 
occur  at  all  or  has  been  very  rarely  observed.  On  the  other  hand,  in  the  specific 
regions  of  distribution  of  the  multilocular  echinococcus,  in  Bavaria,  Würt- 
temberg, and  Northern  Switzerland,  the  hydatid  form  is  quite  rare.     In  conse- 


ECHINOCOCCUS   DISEASE  529 

quence  of  Posselt's  very  interesting  investigations,  I  incline  more  and  more 
to  the  view  that  there  are  two  forms  of  tenia  echinococcus. 

I  should  like  here  to  refer  to  the  fact  that  hone  echinococci.  which  in  their 
distribution  show  great  similarity  to  the  multilocular  echinococcus,  are  fre- 
quently identified  with  these.  In  hone  echinococcus  we  are  dealing  with  the 
exogenous  proliferation  of  small  and  very  small  cysts  deposited  close  beside 
each  other;  but,  besides  these,  there  are  also  larger  cysts  with  encapsulated 
daughter-cysts  in  the  surrounding  soft  parts.  Xow  such  larger  cysts  with 
daughter-cyst  formation  are  a  characteristic  of  the  hydatid  form  in  which  it 
differs  markedly  from  the  multilocular  form.  For  this  reason  it  cannot  be 
assumed  that  every  osseous  echinococcus  belongs  to  the  multilocular  form. 

.  Besides  being  found  in  man.  the  echinococcus  has  been  noted  particularly 
in  the  lung  and  the  liver  of  sheep,  in  cattle,  and  in  pigs;  more  rarely  in  the 
dog,  the  cat,  the  mule,  the  horse,  the  zebra,  the  dromedary,  the  camel,  the 
giraffe,  etc. 

Since  it  has  been  demonstrated  with  certainty  that  the  echinococcus  Cysti- 
cercus occurring  in  man  and  his  domestic  animals  represents  one  and  the  same 
tape-worm,  there  can  no  longer  be  any  question  as  to  the  propagation  of  echino- 
coccus  disease  in  animal  and  man — that  the  dog  takes  up  the  grown  cysticerci 
which  develop  in  the  domestic  animals.  The  possible  modes  of  dissemination 
of  echinococcus  disease  in  any  country  will  therefore  depend  upon  the  number 
of  its  dome-tic  animals,  and  the  distribution  of  the  echinococcus  pest  among 
them.  A-  a  matter  of  fact,  those  countries,  such  as  Iceland.  Victoria,  Mecklen- 
burg and  New  Pomerania,  in  which  the  echinococcus  occurs  most  frequently, 
are  noted  for  an  excessively  large  number  of  animals,  particularly  cattle.  A 
number  of  year-  ago  I  endeavored  to  investigate  the  distribution  of  this  para- 
sitic disease,  and  from  the  reports  of  52  slaughter-houses  I  decided  that  the 
echinococcus  occurs,  upon  the  average,  in  1(>.*'.»  per  cent,  of  cattle,  in  9.83  per 
cent,  of  -beep,  and  in  6.47  per  cent,  of  pigs.  Pomerania  and  Mecklenburg  in 
Germany  are  first  in  the  frequency  of  the  echinococcus  disease.  In  Greifswald 
the  dissemination  of  the  pest  i-  enormous.  In  one  period  of  sis  months  ii.8.58 
per  cent,  of  cattle.  51.02  per  cent,  of  -beep,  and  L93  pei-  cent,  nf  pigs  Were 
found  diseased.  The  conditions  are  similar  in  Mecklenburg.  From  my  pre- 
vious investigations  I  have  concluded  that  ihr  prevalence  of  Ihr  echinococcus 
infection  in  the  inhabitants  of  "  country  is  in  proportion  I"  the  distribution  of 
Ihr  echinocoa  us  pest  among  its  domestic  animals. 

In   man.  a-    well    a-   in   domestic  animal-,   the  dog   i-   the   usual,   if  not   the 

only,  transmitter  of  the  infectious  germ.     The  greater  the  number  of  dogs 

in  any  infected  country,  the  greateT  the  danger  of  contagion.  In  my  own 
vicinity,  the  number  of  dogs,  particularly  in  the  rural  districts,  is  very  great. 
Apart  from  hunting  dogs  and  shepherd  dogs,  almost  every  family  posst 
a  house  dog.  lb'  accompanies  hi-  master  a-  he  work-  about  the  farm,  espe- 
cially when  milking  cows,  which  in  the  summer  occurs  twice  during  the  day, 
hence  he  ha-  repeated  opportunities  to  vi-it  the  grazing  «attic,  and  to  deposit 
hi-  feces  upon  the  field.  Here,  on  the  -mall  grazing  places,  the  focus  of  infec- 
tion mu-t  he  sought  for  the  grazing  cattje,  which  remain  here  for  months,  by 
day  and   by  night 


530  THE  ANIMAL  PARASITES  OF  MAN 

But  how  does  the  dog  become  infected?  Every  one  who  lias  made  observa- 
tions in  the  rural  districts  knows  perfectly  well.  The  butchers  as  well  as  the 
shepherds — the  latter,  as  a  rule,  performing  the  duty  of  slaughter  in  the  coun- 
try— are  familiar  with  the  danger  of  the  echinococcus.  Any  one  who  has  been 
in  a  farming  country  at  slaughter  time  knows  that  the  parts  of  the  meat  which 
are  unsuitable  for  human  food,  among  these  frequently  the  liver  and  the  lungs 
which  are  permeated  with  echinococci,  are  used  as  food  for  the  dogs.  Where 
there  is  careful  management,  organs  of  this  kind  are  buried,  but  rarely  so  deep 
that  the  dog  who  sniffs  about  cannot  finally  reach  them.  A  vicious  circle  is 
formed :  the  infected  cattle,  sheep  and  swine  furnish  the  scolices  to  the  dog ; 
the  dog  furnishes  the  ova  of  the  tenia. 

If  we  observe  the  frequently  intimate  relation  of  children  as  well  as  adults 
with  dogs,  and  how  the  dog  will  lick  the  face  and  the  hands,  we  can  scarcely 
doubt  that  in  this  way,  as  well  as  by  kissing,  infection  can  be  conveyed.  Dogs 
of  every  species  sniff  at  their  own  ani  as  well  as  at  those  of  other  dogs ;  often 
they  carry  around  upon  their  noses  collections  of  mature  proglottides  without 
these  being  noticed  on  account  of  their  diminutive  size.  Toys  which  small 
children  often  lick,  pieces  of  bread  scattered  about  in  different  corners  of  the 
nursery,  may  readily  become  contaminated  by  the  mature  eggs  of  the  tenia. 
The  dogs  probably  discharge  the  mature  proglottides  with  the  feces.  In  the 
feces  of  other  dogs  they  are  fond  of  sniffing  around.  Thus  the  dog's  nose 
becomes  contaminated,  and  the  transmission  of  the  ova  of  the  tenia  may  occur. 
Frequently  the  dog's  feces  are  discharged  in  the  vicinity  of  pumps  and  wells. 
The  proglottides  and  their  ova  continue  to  live  for  a  long  time  on  account  of 
the  moisture  here  constantly  present,  so  that  they  reach  the  human  stomach 
with  the  drinking-water  as  a  still  germinating  brood.  The  teniae  may  also  be 
readily  distributed  by  means  of  vegetables  that  are  eaten  raw,  such  as  lettuce, 
cabbage,  berries  and  fruits  which  grow  upon  the  earth.  The  number  of  ways 
in  which  an  infected  material,  or  the  eggs  of  the  tenia,  finally  reach  the  intes- 
tinal tract  of  man  is  infinitely  great,  and  it  is  unnecessary  to  presuppose  an 
intimate  association  of  the  infected  individual  with  dogs. 

The  number  of  children  infected  appears  very  small  when  we  consider  the 
fact  that  at  this  period  of  life,  in  consequence  of  close  association  with  dogs, 
they  are  particularly  endangered.  This  observation  is  confirmed  by  all  statis- 
tics. In  the  Pomeranian  investigation,  among  139  patients  only  13  were  under 
fifteen  years  of  age.  The  majority  of  infections  occur  between  the  twentieth 
and  fortieth  years  of  life.  Probably  in  consequence  of  the  slow  development 
of  the  echinococcus  in  the  human  organism,  the  germs  acquired  in  youth,  as 
a  rule,  produce  definite  symptoms  only  in  later  years.  That  the  course  may 
be  chronic  is  shown  by  my  collection  of  cases.  Among  others,  a  midwife,  aged 
sixty,  from  her  twenty-fifth  year  (therefore  for  thirty-five  years)  had  period- 
ically coughed  up  echinococci.  A  farmer,  aged  forty,  mentioned  as  the  prob- 
able period  of  invasion  the  time  from  his  ninth  to  his  twelfth  year,  since 
during  this  period  he  always  slept  in  a  bed  with  several  dogs.  He  had  suf- 
fered since  his  thirty-fifth  year  with  frequent  and  repeated  attacks  of  irrita- 
tive cough  with  expectoration  that  contained  echinococcus  cysts. 

It  is  difficult  to  find  proof  from  the  statistics  of  Mecklenburg  and  Pome- 


ECHINOCOCCUS   DISEASE  531 

rania  that  certain  customs  and  habits  of  the  people,  their  sex,  social  condition 
and  occupation,  their  residence  in  the  city  or  in  the  country,  create  a  special 
predisposition  to  acquire  the  parasites.  Echinococcus  disease  represents  a 
slow,  often  insidious  process,  running  its  course  for  several  decade-,  and  the 
occasional  cause,  the  place  and  time  of  infection,  cannot   be  determined. 

In  the  majority  of  cases  only  one  organ  is  attacked.  Unilocular  echino- 
coccus  disease  most  frequently  has  its  seat  in  the  liver.  Tf  several  organs  are 
attacked — ecliinococcus  multiplex — the  liver  is  found  to  lie  one  of  the  organs 
affected. 

Several  series  of  statistics  have  been  compiled  with  regard  to  the  frequency 
of  "dog  tape-worm."  These  indicate  clearly  that  the  liver  is  the  organ  most 
frequently  affected;  in  the  Mecklenburg  investigation  there  were  69  per  cent. 
of  -iieh  cases,  in  that  of  Pomerania.  07.33  per  cent.  As  the  next  organ  to 
he  implicated,  the  lung  may  he  mentioned,  showing  1  1.!»  per  cent,  and  10. G  per 
cent.,  following  this  the  kidneys  with  3.5  per  cent,  and  4.G  per  cent. 

The  abdominal  cavity,  skin,  and  musculature  are  also  quite  frequently 
attacked,  that  is,  in  about  0  per  cent,  of  cases;  but,  in  fact,  any  organ  may 
be  the  -eat  of  an  cchinococcus  cyst.  The  view  that  traumatism  favors  the 
accumulation  of  the  infectious  agents  may  prohahly  he  due  to  the  fact  that 
after  injuries  the  echinococci,  which  until  then  have  been  latent,  manifest  clin- 
ical symptoms.  The  conditions  are  certainly  different  with  the  appearance  of 
multiple  echinococci,  especially  in  the  abdominal  cavity.  The  opinion  that  the 
simultaneous  invasion  of  many  organisms  may  here  he  the  cause  will  often 
prove  correct.  Bui  another  mode  of  developmenl  may  also  he  observed  : 
namely,  autosemination  after  puncture  or  rupture  of  an  echinococcus  Bac. 
Since  v.  Volkmann  first  called  attention  to  this  danger,  I  have  observed  it 
clinically  in  many  cases.  The  colonizing  and  propagation  of  cysts  in  the 
abdominal  cavity  ha-  been  absolutely  proven  by  the  experiments  of  Riemann 
under  the  direction  of  Garre.  Similar  experiments  undertaken  by  other  inves- 
tigators ami  by  myself  failed  of  success,  for  some  unknown  reason.  Either  on 
account  of  the  danger  <>(  disseminating  the  echinococcus  parasite,  or  because 
of  the  toxicity  of  the  echinococcus  fluid,  exploratory  puncture  ha-  fallen  into 
disuse. 

The  danger  that  the  subsequent  oozing  of  the  echinococcus  fluid  from  the 
point  of  puncture  may  bring  about  serious  accident-  and  even  death  has  been 
demonstrated  by  mimerous  observations.  The  appearance  of  urticaria  after 
aspiration  i-  a  not  infrequent  occurrence.  In  a  patient  in  Mosler's  clinic,  a 
\'rw  hour-  after  the  aspiration  of  an  echinococcus  of  the  liver,  an  eruption 
of  urticaria  appeared,  booh  followed  by  cyanosis  and  dyspnea.  <>nlv  after  the 
lap-e  of  several  hour-  did  the  threatening  symptoms  disappear.  Other  authors 
report  the  appearance  of  fever,  singultus,  nausea,  arthritic  pain-,  etc.  A 
patient  of  Jenkins's  died  with  these  symptoms;  Martineau  and  Bryant  report 
similar  cases.  Experimental  investigations  also  confirm  the  view  that  the 
echinococcic  fluid   may  have  a  toxic  action.     Brieger,  for  instance,  isolated 

among  other  -ul>-taiice-  one  which  he  obtained  in  the  form  of  -all  of  platinum, 
and,  after  separating   it    from   the   metal,  he  injected   it    in   solution    into   mice 

with  rapidly  fatal  result.     Aspiration  i-  not  advisable,  unless  the  radical  oper- 


532  THE  ANIMAL  PARASITES  OF  MAN 

ation  be  performed  immediately  after  the  exploratory  puncture ;  indeed,  it  is  a 
quest  inn  whether  aspiration  should  be  performed  at  all. 

Echinococcus  disease  is  not  always  easy  to  diagnosticate.  Frequently  at 
the  autopsy,  in  the  liver  or  other  organs,  cysts  the  size  of  a  child's  head  and 
even  larger  are  found  which  had  not  produced  the  slightest  symptoms  during 
the  life  of  the  patient.  The  gravity  of  the  disease  depends  upon  the  location 
of  the  cyst,  the  size,  the  effect  upon  neighboring  organs,  and,  possibly,  the 
purulent  character  of  the  contents  of  the  cyst.  Should  it  suppurate,  small 
echinococcus  cysts  in  the  brain  and  spinal  cord  may  cause  severe  symptoms; 
on  the  contrary,  occasionally,  large  sacs  which  have  no  deleterious  effect  upon 
the  surrounding  area  exist  for  a  long  time  without  giving  rise  to  serious  symp- 
toms.    In  general,  the  symptomatology  may  be  described  as  follows : 

SYMPTOMS 

The  embryo  which  has  entered  the  body  causes  a  reaction  of  the  tissue 
which  leads  to  the  formation  of  the  wall  of  a  cyst.  With  continued  growth 
the  effect  of  pressure  upon  the  neighboring  tissue  becomes  apparent,  and 
decided  disturbances  in  circulation,  secretion  and  excretion  are  manifest. 
Particularly  dangerous  is  the  development  of  the  echinococcus  in  cavities 
where  the  growing  tumor  cannot  fail  to  cause  serious  disturbance,  as  for  in- 
stance in  the  pelvis,  by  compression  of  the  organs  situated  in  this  region. 
When  the  development  of  the  echinococci  occurs  in  the  respiratory  tract,  the 
symptoms  there  are  also  severe.  The  symptoms,  however,  become  especially 
threatening  if  suppuration  supervene,  or  the  contents  of  the  cyst  should  per- 
forate its  walls.  If  the  contents  of  the  cyst  be  emptied  into  the  abdominal  or 
thoracic  cavities,  fatal  disease  usually  follows.  When  there  is  adhesion  among 
neighboring  organs,  after  penetrating  the  wall  of  the  cyst  the  parasite  enters 
these,  and  permeates  them  in  the  same  way  as  the  organs  primarily  affected. 
Thus  the  parasite  traverses  remarkably  great  distances.  The  course  is  most 
favorable  when  perforation  occurs  through  the  skin.  Discharge  into  the 
stomach  and  intestine  and  into  the  pelvis  of  the  kidney,  into  the  bladder  or 
into  the  vagina  is  relatively  favorable.  A  cyst  of  this  kind  may  very  readily 
become  the  starting  point  of  a  fatal  pyemia.  Perforation  into  the  trachea, 
into  the  bronchi,  and  particularly  into  the  circulatory  system  is  always  most 
serious.     Echinococcus  of  the  superficial  organs  runs  a  less  dangerous  course. 

The  general  condition  of  the  patient  is  usually  most  affected  when  the 
echinococcus  exerts  an  influence  upon  the  neighboring  organs  by  its  size,  or 
when  suppuration  occurs.  Only  after  attention  has  been  thus  called  to  the 
atfection  does  the  patient  seek  professional  aid.  A  number  of  conspicuous 
phenomena,  such  as  the  slow,  steady,  painless  growth  of  the  tumor,  the  absence 
of  cachexia,  the  uniform  roundness  of  the  tumor,  the  smooth  surface,  the 
absence  of  fever,  the  elasticity,  the  presence  of  fluctuation,  and  the  possible 
demonstration  of  a  hydatid  thrill,  in  general  favor  the  existence  of  an  echino- 
coccus sac.  By  a  hydatid  thrill  we  mean  that  sensation  which  the  tumor  con- 
veys to  the  percussing  finger  or  to  the  palpating  hand,  a  sensation  similar  to 
that  obtained  by  pressing  upon  a  cushion  with  springs.    The  cause  of  the  hyda- 


ECHINOCOCCUS   DISEASE  533 

tid  thrill  appears  to  be  the  waves  of  the  fluid  contents  of  the  cyst ;  it  is,  there- 
fore, to  a  certain  extent  only  a  distinct  fluctuation.  This  condition  also  occurs 
in  cysts  of  the  ovaries,  in  ascites,  etc.  Santini  and  Rovighi  have  observed 
that  the  echinococcu-  cysts,  besides  the  hydatid  thrill,  convey  also,  upon  simul- 
taneous percussion  and  auscultation,  a  characteristic,  deep,  sonorous  tone,  the 
so-called  hydatid  resonance.  This  phenomenon  is  said  not  to  be  present  in 
deep  seated  cysts  with  thickening  and  degenerating  walls.  The  size  and  extent 
of  the  cyst,  as  was  demonstrated  by  Manasse  in  a  case  of  renal  echinococcus, 
may  be  determined  by  the  Röntgen  rays.  Confusion  of  the  echinococcus  cyst 
with  other  tumors  or  abscesses,  such  as  cystic  degeneration  of  the  kidney-, 
ovarian  cysts,  tumors  of  the  uterus,  tumors  of  the  omentum,  of  the  pancreas, 
subphrenic  abscesses,  etc.,  can,  of  course,  never  be  entirely  avoided.  In  spite 
of  the  most  minute  examination  of  the  history,  of  the  results  of  inspection, 
of  palpation,  and  of  percussion,  and  of  the  relation  of  the  tumor  to  neighbor- 
ing organs,  the  diagnosis  in  some  cases  cannot  be  made  with  absolute  certainty 
unless  some  definite  points  of  support  are  obtained  by  rupture  of  the  cyst 
and  an  admixture  of  its  contents  with  the  sputum,  with  the  vomitus,  with 
the  contents  of  the  intestines,  and  with  the  urine.  In  cases  which  offer  great 
diagnostic  difficulty,  an  exploratory  puncture  may  at  once  clear  the  entire 
clinical  picture  by  the  recognition  of  a  fluid  which  is  non-albuminous,  and 
which  contains  scolices  or  booklets.  But  the  danger  of  this  process  will  cer- 
tainly always  limit  it-  use  in  diagnosis. 

The  prognosis  depend-;  upon  the  location,  the  size,  and  the  relation  of  the 
echinococcus  cyst  to  its  surroundings.  Although  a  benign  tumor  in  itself, 
it  may.  particularly  by  suppuration,  lead  to  phenomena  which  endanger  life. 
In  multiple  echinococci  the  prognosis  is  correspondingly  more  unfavorable. 

TREATMENT 

Prophylactic  measures  musl  be  premised  with  a  caution,  which  cannot  be 
too  emphatically  expressed,  against  intimate  association  with  dogs.  In  infected 
regions  their  number  should  be  limited  as  much  as  possible.  Whether  methodic 
tape-worm  cures,  on  account  of  the  perhaps  brief  parasitism  of  the  tenia  in 
the  dog,  are  of  any  use,  is  doubtful.  On  the  contrary,  the  important  point 
in  prophylaxis,  it  appears  to  me,  is  to  protect  the  dogs  from  acquiring  the 
tenia  echinococcus.  This  may  be  best  attained  by  the  introduction  of  the 
compulsory  inspection  of  meat.  All  organs  infected  with  echinococci  must  be 
destroyed  by  cremation.  Meat  inspection  in  the  country  districts  among  cattle 
raisers  is  not  likely  to  find  favor  when  they  learn  that  annually  in  Prussia 
about  .sMi  cattle  directly  succumb  to  the  echinococcus  pest.  The  indirect  harm 
arising  from  this  is  that  animal-  infested  with  echinococcu-  suffer  in  their 

nutrition,  and  are  prematurely  slaughtered,  and  this  may  be  an  important  point 

in  agriculture. 

Internal  treatment  i-  ineffectual,  and  successive  punctures  with  aspiration 
of  the  content-  as  well  as  injection-  of  medicated  fluids  should  be  rejected 
for  the  above-ment  ioned  reasons. 

On  principle  I  am  opposed  to  the  method  introduced  by  Baccelli  of  iniec- 


534  THE  ANIMAL  PARASITES   OF  MAN 

tions  of  corrosive  sublimate,  although  a  number  of  cases  have  been  reported 
with  favorable  results.  The  process  consists  in  aspiration  of  the  cyst  contents 
with  a  succeeding  injection  of  a  1-1,000  corrosive  sublimate  solution.  I  have 
seen  recovery  occur  after  puncture,  even  without  injection  of  drugs,  but  much 
more  frequently  suppuration  followed  and  finally  made  laparotomy  necessary. 
Recovery  through  surgical  means  can  only  take  place  by  the  removal  of  the 
echinococcus  sac. 

The  seat  of  the  diseases  is  usually  the  liver.  For  this  reason  I  should  like 
briefly  to  describe  the  treatment  of  echinococcus  of  the  liver.  Madelung  de- 
fines extirpation  of  the  cyst  including  the  capsule  as  the  unquestioned  "  ideal  " 
method  of  treatment.  If  of  moderate  size,  with  a  superficial  seat,  and  there 
is  no  suppuration,  this  operation  will  bring  about  the  best  results.  In  the 
majority  of  cases,  the  choice  between  a  radical  operation  or  one  performed  at 
two  different  times  comes  into  question.  If  danger  is  present,  the  single  or 
less  radical  operation  is  to  be  preferred  on  account  of  its  greater  rapidity. 
This  is  also  recommended  if  the  cyst  is  insufficiently  exposed  in  the  field  of 
operation,  or  if,  with  multiple  cysts,  after  the  removal  of  one  cyst  the  others 
are  more  easily  reached.  The  method  also  by  which  an  incision  is  made  has 
the  advantage  of  being  less  dangerous.  As  a  rule,  this  method  is  resorted  to 
if  there  are  no  special  indications  for  more  rapid  interference. 

Multilocular  echinococcus  has  in  only  a  few  cases  been  treated  by  opera- 
tion ;  namely,  by  Brunner,  Terillon  and  Brims.  The  latter  advises  cuneiform 
excision.  Only  the  smaller  multilocular  echinococci  can  be  successfully  re- 
moved by  operation. 

ECHINOCOCCI  OF  VARIOUS  ORGANS 

I  shall  briefly  review  the  echinococci  found  in  different  organs : 
Echinococci  of  the  brain  are  rare.  Davaine  mentions  32,  Neisser  68  cases. 
Upon  the  whole  about  90  cases  are  known,  and  among  these  is  one  case  of 
multilocular  echinococcus.  Usually  the  parasite  is  solitary.  It  is  generally 
of  moderate  size.  The  cysts  are  situated  in  the  white  as  well  as  in  the  gray 
substance,  and  are  surrounded  by  connective  tissue  capsules;  the  neighboring 
cerebral  substance  is  anemic,  partly  atrophic.  After  a  fairly  prolonged  time 
of  growth  a  hemisphere  may  resemble  a  sac  with  thick  walls.  Several  times 
after  penetrating  the  skull,  growth  and  discharge  externally  through  the  nose, 
ear,  etc.,  have  taken  place.  Westphal  observed  a  case  in  which  about  90  cysts 
were  discharged.  The  seat  and  the  size  of  the  tumor  .determine  the  symp- 
toms. General  cerebral  and  focal  phenomena  appear  until  we  have  the  symp- 
toms of  cerebral  tumor.  The  diagnosis  of  the  nature  of  the  tumor  will  be 
possible  only  when  echinococcus  disease  of  another  organ  is  present,  or  if,  in 
the  course  of  the  disease,  external  perforation  occurs.  If  the  nature  of  the 
tumor  and  the  localization  of  its  seat  are  determined,  surgical  treatment  may 
be  successful.     In  the  main  the  prognosis  is  unfavorable. 

K<  hinococcus  of  the  spinal  cord  is  even  rarer  than  that  of  the  brain.  About 
22  cases  in  all  are  known.  Usually  the  parasite  is  found  between  the  dura 
and  the  vertebra,  more  rarely  in  the  dural  sac ;  or  it  may  develop  in  the  verte- 


ECHINOCOCCUS   DISEASE  535 

bra  itself,  penetrating  externally  or  internally.  In  some  cases  the  parasite  grows 
outwardly  into  the  vertebral  canal.  Maguire  mentions  two  cases  in  which  the 
parasite  developed  in  the  spinal  cord  itself. 

The  symptoms  are  those  of  compression.  The  first  phenomena  frequently 
arise  from  disease  of  the  vertebra,  and  from  compression  of  the  nerve  trunks. 
The  symptoms  develop  gradually,  and  resemble  those  of  a  compression  myelitis. 
The  entire  absence  of  pain  and  the  free  movability  of  the  vertebral  column  are 
conspicuous;  this,  however,  may  also  be  the  case  in  tumors.  Diagnosis  be- 
comes possible  when  the  parasite  appears.  The  prognosis  has  usually  been 
unfavorable.  In  the  case  reported  by  Szkekeres,  operation  was  attempted  after 
a  piece  of  bone  one-half  a  centimeter  in  length  had  been  exfoliated. 

Echinococcus  of  the  orbit.  Echinococcus  of  the  eye-ball  has  as  yet  not 
been  determined  with  certainty,  and  echinococcus  of  the  orbit  is  also  rare. 
Krämer  has  collected  08  and  Golowin  93  observations.  To  these  may  be  added 
the  cases  of  Ziegler,  Wagenmann  and  Blaschek.  It  is  noteworthy  that,  accord- 
ing to  Krämer,  the  disease  occurs  three  times  as  frequently  in  men  as  in  women. 
In  two-thirds  of  the  cases  the  patients  were  between  the  eleventh  and  twenty- 
first  years  of  life.  As  a  rule,  the  echinococcus  develops  primarily  in  the  orbit. 
in  rarer  cases  it  finds  it  way  into  neighboring  organs  after  destruction  of  the 
wall  of  the  orbit.  The  parasite  is  found  in  both  orbits  with  about  the  same 
frequency,  and  almost  always  in  the  base;  rarely  in  the  anterior  lateral  parts. 
The  development  is  usually  insidious,  seldom  fulminant.  The  first  symptoms 
are  commonly  pain  and  the  development  of  an  exophthalmos.  The  conjunc- 
tiva and  lids  become  inflamed.  Decrease  in  motion  of  the  bulbus  oculi,dis- 
turbances  of  vision,  and  loss  of  sight  in  varying  grades  appear  gradually. 
Suppuration  is  not  rare.  In  cases  in  which  no  operation  is  performed,  early 
atrophy  of  the  optic  nerve,  necrosis  of  the  cornea,  and  panophthalmia  occur. 
The  diagnosis  is  often  very  difficult.  Confusion  with  malignant  neoplasms 
has  several  times  Led  to  enucleation.  Krämer  caution-  na  againsl  exploratory 
puncture  on  account  of  the  danger  of  confounding  the  condition  with  that  pro- 
duced by  an  encephalocele.  The  slow  development  of  a  tumor  in  the  orbit 
without  fever,  severe  pain  deep  in  the  orbital  cavity,  a  tumor  with  distinct 
or  indistinct  fluctuation,  and  the  early  appearance  of  disturbances  of  sight  are 
all  strongly  indicative  of  echinococcus.    The  treatment  is  surgical. 

The  echinococcus  has  been  twice  observed  in  the  frontal  sinus,  which  had 
raptured  into  the  orbit. 

In  the  nose,  in  the  oral  cavity,  in  the  tongue,  in  the  gums,  in  the  pharynx 
and  in  the  parotid  the  echinococcus  has  also  occasionally  been  observed. 

Echinococcus  in  the  neck  is  a  rare  occurrence.  Güterbock  has  collected 
26  cases  of  this  kind.  Besides  these  I  found  cases  recently  published  by  Reich, 
Jürgens,  Thevenot  and  Steinbrück.  Tbc  parasite  generally  chooses  as  it-  seat 
the  region  of  the  external  border  of  the  sternocleidomastoid;  this  without 
doubt  account-  for  it-  originating  in  the  Bheaths  of  the  Large  vessels  of  the 
neck.  The  echinococcus  sac  Blowly  raises  the  sternocleidomastoid  and  appears 
at  the  interna]  border  of  the  muscle  as  a  small  tumor,  while  the  Larger  portion 
of  the  sir  is  situated  upon  the  external  border.  The  connection  of  both  tumors 
is  proven  by  the  continuance  of  the  fluctuation.     Later,  with  increased  growth, 


536  THE  ANIMAL  PARASITES   IN  MAN 

the  characteristic  tabulated  tumor  disappears.  Decided  displacements  of  the 
organs  of  the  neck  may  develop  in  such  cases.  Confusions  may  arise  from 
echinococci  which  are  situated  in  the  muscle  itself  or  that  have  developed  in 
the  thyreoid  gland.  In  three  cases  after  successful  extirpation  death  resulted 
from  secondary  hemorrhage. 

Echinococcus  of  the  thyreoid  gland  is  rare.  Henle  reports  18  cases;  in 
three  other  cases  the  diagnosis  is  questionable.  Vitrac  has  collected  21  re- 
ports of  echinococcus  of  the  thyreoid.  Another  case  is  reported  by  Posadac. 
The  echinococcus  is  usually  unilocular  and  may  attain  the  size  of  a  fist.  In- 
creasing growth  causes  atrophic  conditions  of  the  glandular  tissue.  The  con- 
sequences of  displacement,  that  is,  compression,  of  the  neighboring  organs, 
in  which  particularly  the  trachea,  the  esophagus  and  the  recurrent  laryngeal 
nerve  are  to  be  considered,  may  be  serious.  Suppuration  of  the  cyst  is  fre- 
quent. The  sac  surrounding  the  echinococcus  becomes  adherent  by  inflamma- 
tion to  the  adjacent  areas,  and  these  are  to  a  certain  extent  involved  in  the  echi- 
nococcus sac,  so  that  this  represents  only  a  part  of  the  echinococcus.  This 
enlargement  results  in  increased  erosion  of  the  surrounding  areas  in  which  the 
trachea  particularly  may  be  implicated.  Adbesions  to  the  muscles  and  the 
skin  are  less  frequent.  The  echinococcus  grows  very  slowly.  Its  form  is  usu- 
ally globular.  The  difficulty  in  respiration  which  occurs,  to  which  difficulty 
in  deglutition  and  paralysis  of  the  recurrent  laryngeal  nerve  may  be  added, 
causes  the  patient  to  consult  a  physician.  The  diagnosis  can  rarely  be  made 
with  certainty.  Early  operation  improves  the  prognosis  decidedly.  Accord- 
ing to  Henle  wide  opening  of  the  sac  is  most  frequently  advisable,  as  enuclea- 
tion is  often  very  difficult.  If  this  operation  be  attempted,  it  is  not  always 
possible  to  spare  the  recurrent  laryngeal  nerve  which  may  be  situated  in  the 
wall  of  the  sac. 

A  case  of  echinococcus  of  the  larynx  has  been  described  by  Schüssler. 

Primary  echinococcus  of  the  pleura  is  rare.  Maydl  and  Winzerling  have 
collected  30  cases  from  literature.  In  these  the  echinococcus  was  situated 
either  between  the  pleura  pulmonalis  and  the  costal  pleura,  in  the  pleural  cav- 
ity, or  external  to  the  pleura  costalis.  Much  more  frequent  are  secondary 
pleural  echinococci  which  have  ruptured  into  the  pleural  cavity  from  neigh- 
boring organs. 

The  echinococcus  is  usually  found  upon  the  right  side,  surrounded  by  a  thin 
wall  of  connective  tissue.  It  generally  attains  great  dimensions.  In  the 
main  the  symptoms  differ  but  little  from  those  of  a  pleurisy  with  effusion. 
The  patients  complain  of  stitch  in  the  side  and  an  irritative  cough,  accom- 
panied by  scant  mucus  expectoration.  Fever  is  absent.  If  the  echinococcus 
is  large  it  leads  to  dilatation  of  the  affected  side  of  the  thorax,  frequently  giving 
a  flaring  shape  to  the  lower  part  of  the  thorax,  with  retardation  or  immobility 
in  respiration.  Percussion  reveals  a  more  or  less  extensive  area  of  dulness, 
frequently  bow-shaped.  Absence  or  diminution  of  the  respiratory  murmur 
and  of  fremitus  is  noted ;  occasionally  bronchial  respiration  is  present.  In 
small  cysts  egophony  and  bronchophony  are  observed.  Neisser  quite  prop- 
erly emphasizes  as  characteristic  the  conspicuous  proximity  of  normal  and 
abnormal  auscultatory  phenomena.     In  right-sided  disease,  the  liver  is  dis- 


ECHINOCOCCUS   DISEASE  537 

placed  downward  and  the  heart  to  the  left.  Left-sided  eehinococci  lead  to 
dislocation  of  the  spleen  and  kidney.  In  bilateral  echinococcus  the  heart  is 
forced  into  the  mediastinal  space.  If  the  echinococcus  has  a  tendency  to  grow 
outwardly  it  forces  its  way  through  the  intercostal  spaces,  leads  to  erosion  of 
the  ribs,  and  appears  as  a  semiglobular  tumor  beneath  the  skin.  The  skin  is 
usually  movable  over  the  tumor,  but  occasionally  adheres  to  it,  and  shows 
decided  inflammation.  Secondary  pleurisy  is  said  to  be  invariably  absent. 
In  the  main,  the  echinococcus  shows  but  slight  tendency  to  perforation.  If 
rupture  occurs,  it  usually  takes  place  through  the  bronchi. 

The  diagnosis  is  mostly  difficult.  Differentiation  from  solid  tumor  is,  how- 
ever, generally  possible.  If  a  collection  of  fluid  can  be  detected,  the  question 
arises  whether  this  is  situated  above  or  below  the  diaphragm.  In  favor  of  a 
subdiaphragmatic  seat  is  the  bell-shaped  prominence  of  the  lower  parts  of  the 
thorax,  and  the  absence  of  the  respiratory  displacement  of  the  liver  downward. 
On  account  of  atrophic  paralysis  of  the  diaphragm  the  upper  bow-shaped 
line  of  dulness  prevents  the  recognition  of  respiratory  displacement.  Besides, 
the  history  usually  points  to  a  disease  of  the  liver.  Yet  in  many  cases  a 
positive  diagnosis  is  almost  impossible.  To  distinguish  echinococcus  from 
pleurisy  with  effusion  is  important.  The  latter  is  accompanied  by  more 
marked  constitutional  and  local  phenomena,  chills,  fever,  cough,  stitch  in  the 
side  and  dyspnea.  Later  the  dyspnea  is  less  marked,  while  in  the  case  of 
echinococcus  it  is  one  of  the  most  prominent  and  troublesome  Bymptoms. 
Pleural  exudates  lead  to  a  uniform  bulging,  pleural  echinococcus  to  a  pro- 
tuberance, of  the  Lower  aperture  of  the  thorax.  In  pleurisy  the  line  of  dulness 
follows  the  well-known  characteristics,  while  in  echinococcus  the  line  of  dul- 
ness -hows  irregularities.  The  demonstration  of  another  tumor  in  the  liver 
is  not  without  importance.  The  course  of  pleurisy  is  much  more  rapid  than 
that  of  the  slowly  growing  echinococcus.  Exploratory  puncture  is  not  advis- 
able on  account  of  the  danger  associated  with  it,  unless  an  immediate  opera- 
tion is  to  follow. 

Echinococcus  of  II"'  lung  is  next  in  frequency  to  thai  of  the  liver.  Ac- 
cording to  Madelung  L1.9  per  cent,  of  all  cases  occurred  in  the  lungs,  and 
according  to  the  Pomeranian  statistics,  10.6  per  cent.  The  parasite  may  de- 
velop in  any  part  of  the  lung;  mosl  frequently,  however,  it  is  met  with  in  the 
right  lower  lohe.  The  latter  circumstance  is  explained  by  the  frequenl  simul- 
taneous affection  of  the  liver.  The  thinness  of  the  walls  of  it-  capsule,  as 
elsewhere,  and  the  yielding  of  the  pulmonary  tissue  make  the  decided  growth 
of  the  echinococcus  possible,  and  it  not  rarely  till-  the  pleural  cavity,  leading 
to  displacement  of  the  heart,  of  the  diaphragm,  the  liver  and  the  spleen.  Symp- 
toms of  chronic  inflammation,  of  hepatization,  of  atrophy,  or  of  gangrene,  may 
develop  and  complicate  the  pathology.  Erosion  of  the  bronchi  and  of  tin1 
pulmonary  vessels,  and  rupture  into  the  pleural  cavity,  are  not  infrequent.  \- 
the  result  of  destruction  of  larger  blood-vessels,  aevere,  often  fatal,  attack-  of 
hemoptysis  occur. 

The  passage  of  daughter-cysts  into  the  blood-vessels  with  the  formation  of 

emboli  ha-  l n  observed.     Upon  opening  into  the  bronchi,  gangrenous  sputum 

appears  in  which  daughter-cysts,  scolices  or  -bred-  of  membrane  are  found. 


538  THE  ANIMAL  PARASITES  OF  MAN 

In  other  cases  the  symptoms  of  pyopneumothorax  develop.  Not  rarely  rup- 
ture into  the  diaphragm  occurs,  and  thus  the  echinococcus  finds  entrance  into 
the  parenchyma  of  the  liver.  Eupture  into  the  intestine  and  into  the  walls  of 
the  abdomen  etc.,  has  also  been  observed.  Secondary  pulmonary  echinococci 
are  rarer  than  primary  ones.  Usually  originating  in  the  liver,  they  penetrate 
the  diaphragm  and  the  pleural  cavity  and  enter  the  lung.  Rupture  into  the 
bronchi  or  into  the  pleural  cavity  produces  severe  symptoms.  The  simul- 
taneous perforation  of  the  biliary  passages  and  the  intestine  has  been  repeat- 
edly observed. 

The  symptoms  for  a  long  time  may  be  indefinite  and  point  only  to  an 
affection  of  the  respiratory  organs.  With  increasing  growth  a  very  trouble- 
some cough  and  attacks  of  dyspnea  usually  occur.  As 
the  first  symptom  I  have  repeatedly  observed  hemop- 
tysis with  cough,  so  that  the  clinical  picture  resembled 
phthisis  pulmonum.  Severe  paroxysms  of  cough  may 
cause  perforation  b}'  the  echinococcus,  mostly  unilocu- 
lar, into  the  bronchi,  and  the  discharge  of  cysts,  large, 
rolled-up  masses  of  membrane  or  shreds  of  membrane 
and  scolices.  The  seat  of  the  disease,  and  sometimes 
even  the  side  which  is  affected  by  the  disease,  may  be 

FlGE?HmocTcTuT  Mem°     difficult  to  recognize,  if  the  cyst  is  centrally  situated 

BRANE  or  is  surrounded  by  a  thick  layer  of  pulmonary  tissue 

containing  air.  Not  rarely,  prior  to  rupture,  suppura- 
tion or  putrefaction  of  the  contents  of  the  cyst  occurs,  and  this  always  takes 
place  after  rupture  of  the  cyst. 

If  the  seat  of  the  echinococcus  is  at  the  periphery  of  the  lung,  especially 
if  it  has  attacked  an  upper  lobe,  the  symptoms  resemble  chronic  pulmonary 
tuberculosis;  but  the  fair  condition  of  nutrition,  in  spite  of  repeated  hemop- 
tysis, and  the  absence  of  the  characteristic  expectoration  are  opposed  to  this 
view.  Occasionally  a  complication  with  tuberculosis  is  present.  Even  when 
the  disease  attacks  a  lower  lobe,  no  signs  are  usually  manifest  other  than 
those  of  a  pleural  effusion.  The  nature  of  the  affection  is  frequently  deter- 
mined only  by  exploratory  puncture,  which  is  performed  with  the  expectation 
of  finding  a  pleural  exudate  or  an  empyema. 

The  prognosis  of  pulmonary  echinococcus  is  serious,  but  by  no  means  abso- 
lutely unfavorable.  In  the  Pomeranian  statistics,  among  16  cases  spontane- 
ous discharge  of  the  cyst  was  followed  by  recovery  in  eight,  and  two  were 
cured  by  operative  treatment.  Death  resulted  from  exhaustion  in  two  cases. 
One  that  was  operated  upon  died.  In  another,  pulmonary  echinococcus  was 
only  an  accidental  autopsy  finding.  Surgical  interference  appears  to  be 
advisable  in  all  cases  in  which  physical  examination  reveals  suppuration  and 
putrefaction  in  the  cyst. 

K'Jtinococcus  of  the  mediastinum  is  uncommon.  About  six  cases  only  are 
on  record.  On  account  of  the  proximity  to  the  heart  and  lungs,  the  echino- 
coccus here  causes  grave  danger. 

Echinococcus  disease  of  the  circulatory  apparatus  is  rare.  According  to 
Huber  about  40  cases  have  been  observed.    To  these  may  be  added  the  cases 


ECHINOCOCCUS   DISEASE  539 

of  Demantke,  Lehne  and  Klehmet.  The  echinococcus  is  usually  unilocular. 
The  right  heart  is  more  frequently  implicated  than  the  left.  The  seat  of  the 
parasite  is  the  heart  muscle,  and  here  it  attains  its  growth.  For  the  most 
part  its  course  is  marked  by  no  symptoms,  at  least  of  parasitism.  The  condi- 
tions are  different,  however,  if  the  distended  cyst  grows  into  the  cardiac 
cavities  and  bursts  its  sac.  The  symptoms  of  cesto-embolism  in  this  case 
do  not  differ  decidedly  from  emboli  as  the  result  of  thrombi.  According  to 
the  size  and  extent  of  the  embolus,  according  to  its  benign  or  malignant 
(putrid)  composition,  and  according  as  the  smaller  or  larger  vessels  are  ob- 
structed, the  disturbances  due  to  emboli  of  cestodens  show  varying  charac- 
teristics. We  should  digress  too  far  if  we  further  discussed  these  extremely 
complicated  conditions.  Death  often  results  suddenly  without  preceding  symp- 
toms. In  some  cases  there  are  antecedent  signs  of  disease  of  the  heart  and 
of  the  lungs;  in  other  cases  death  takes  place  after  a  long  illness  with  com- 
plications such  as  perforation  and  embolism  of  daughter-cysts. 

In  emboli  into  the  greater  circulation  the  perforating  cysl  is  usually  situ- 
ated in  the  left  heart,  or  the  cysts  develop  from  a  pulmonary  echinococcus 
which  has  burrowed  into  the  pulmonary  vein.  Death,  as  a  rule,  occurs  sud- 
denly. It  may  be  readily  understood  that  such  cases  as  these  are  rarely 
under  clinical  observation  for  a  long  time;  the  disease  is  found  at  the  autopsy 
in  cases  where  death  has  occurred  suddenly. 

Echinococcus  of  the  blood-vessels  and  lymph-vessels  as  well  as  of  the  peri- 
cardium is  extremely  rare. 

Echinococcus  of  the  liver  is  the  form  most  frequently  met  with.  In  the 
Mecklenburg  statistics  they  amounted  to  G9  per  cent,  of  all  observed  cases, 
in  the  Pomeranian  statistics  to  67.33  per  cent.  They  are  for  the  most  part 
unilocular,  rarely  multiple.  They  are  found  in  all  parts  of  the  liver,  but 
most  frequently  in  the  right  lobe.  When  centrally  situated  the  cysl  grows 
but  slowly,  while  echinococci  peripherally  situated  give  rise  to  greal  enlarge- 
ment of  the  organ,  even  to  sis  or  -even  times  its  normal  size.  The  liver 
substance  is  ruptured,  and  the  cyst  appears  with  single  and  multiple  semi- 
globular  elevations  upon  the  surface.  It'  the  echinococcus  develops  upon  the 
convex  surface  it  forces  the  diaphragm  far  up  into  the  pleural  cavity,  and 
causes  compression  of  the  lung  and  displacement  of  the  heart. 

Occasionally  the  echinococcus  penetrates  the  diaphragm  and  extends  into, 
or  perforates  into,  the  pleural  cavity  or  the  bronchi.  When  the  cysl  spreads 
into  the  abdominal  cavity,  it  causes  displacement  of  the  Btomach  and  intes- 
tines. It  occasionally  adhere-  to  these  organs,  and.  anally,  ruptures  into 
them;  or,  in  the  absence  of  adhesions,  it  may  perforate  the  abdominal  cavity. 
This  is,  however,  rare.  In  Buch  cases  fatal  peritonitis  is  the  immediate  con- 
sequence, while  with  rupture  into  the  Btomach,  intestines,  etc.,  ultimate  recov- 
ery is  possible.  The  paths  which  the  echinococci  may  make  for  themselves 
are  numerous. 

Echinococci  of  smaller  Bize  often  produce  no  symptoms,  or,  at  least,  not 
for  a  long  time.  Usually  only  with  increasing  growth  does  the  parasite  mani- 
fest its  presence.  Symptoms  are  at  first  local,  such  as  b  Bense  of  pressure, 
of  heaviness,  or  occasionally  pain.    Frequently  echinococci  of  considerable  size 


540  THE  ANIMAL  PARASITES  OF  MAN 

are  seen  which  have  grown  almost  without  symptoms.  They  finally,  however, 
lead  to  displacement  of  adjacent  organs,  particularly  of  the  lung  and  the 
heart,  and  a  prominence  appears  in  the  hepatic  region  and  in  the  lower  parts 
of  the  thorax.  Protuherances  from  the  size  of  an  apple  to  that  of  a  child's 
head  are  not  rare,  and  they  may  be  recognized  by  inspection  and  palpation. 
Palpation  is  almost  always  painless.  Hydatid  thrill,  a  symptom  which  has 
been  mentioned  so  often,  is  occasionally  present,  I  have  only  rarely  been 
able  to  elicit  it.  Jaundice  is  by  no  means  frequent.  As  the  size  of  the  tumor 
increases  it  gives  rise  particularly  to  gastric  difficulty :  disturbance  of  appetite, 
nausea,  a  tendency  to  vomit,  constipation.  Dyspnea,  cough,  attacks  of  fear, 
cardiac  palpitation,  etc.,  also  occur. 

While  the  course  has  previously  been  afebrile,  when  suppuration  of  the 
cyst  occurs  high  fever,  chills,  and  great  pain  appear,  and,  if  suppuration  be 
long-continued,  pyemic  phenomena  in  the  lungs,  spleen  and  kidneys  may  bring 
a  threatening  change.  Rupture  into  the  pleural  cavity,  into  the  lungs,  and 
into  the  abdominal  cavity  may  also  give  rise  to  a  condition  of  collapse,  pyo- 
pneumothorax, peritonitis,  etc.,  and  may  seriously  endanger  the  life  of  the 
patient.  Or  perforation  into  the  stomach  or  intestine  may  lead  to  vomiting 
or  discharge  of  the  characteristic  contents  of  the  cyst.  Rupture  into  the 
biliary  passages  we  have  several  times  known  to  cause  the  discharge  of  bile- 
stained  cysts  or  shreds  of  membrane  with  the  symptoms  of  a  colitis  hepatica. 

In  rare  cases  the  echinococcus  is  felt  beneath  the  abdominal  walls  far 
removed  from  its  original  seat,  and  here  finally  leads  to  rupture. 

The  course  described  is  not  invariable  in  echinococcus  disease.  Fortu- 
nately, the  echinococcus  not  seldom  develops  to  only  moderate  size.  It  dies, 
the  sac  contracts,  and  the  contents  are  absorbed.  Calcareous  nodes  and  broken 
cheesy  masses  in  which  portions  of  the  echinococcus  may  be  recognized  are 
occasional  autopsy  findings.  In  the  Pomeranian  report,  compiled  by  Wiede- 
mann at  my  instigation,  and  including  more  than  153  cases,  echinococcus 
of  the  liver  occurred  31  times  =  33.01  per  cent,  as  an  accidental  autopsy 
finding. 

The  same  compilation  gives  data  concerning  the  prognosis  of  echinococcus 
cases.  In  28  instances  there  was  no  operative  treatment,  Twelve  patients 
died  of  chronic  invalidism.  Spontaneous  recovery  by  perforation  into  the 
lung  and  intestine  occurred  in  8  patients.  In  8  other  cases  the  further  course 
was  unknown.  In  41  operative  cases  recovery  followed  in  31  =  82.92  per 
cent.     Improvement  occurred  in  4  =  9.75  per  cent.;  3  died  =  7.31  per  cent. 

In  the  differential  diagnosis,  besides  amyloid  fatty  liver  and  hypertrophic 
cirrhosis — diseases  which  are  sufficiently  characterized  by  the  accompanying 
symptoms — we  must  consider:  Hepatic  abscess,  cancer  of  the  liver,  syphilis 
of  the  liver,  dropsy  of  the  gall-bladder,  hydronephrosis,  etc. 

Lennhof  calls  attention  to  a  symptom  he  observed  in  cysts  of  the  lower 
part  of  the  liver — an  "inspiratory  furrow."  Upon  deep  inspiration,  accord- 
ing to  his  observation,  the  prominence  of  the  abdomen  due  to  the  tumor  moves 
downward  while  the  skin  retracts  above  this,  and  between  the  arch  of  the 
ribs  and  the  prominence  a  flat  furrow  is  formed. 

Abscess  of  the  liver  usually  develops  acutely,  and  is  accompanied  by  a  chill, 


ECHINOCOCCUS  DISEASE  541 

by  decided  pain  and  rapid  loss  of  strength.  Differentiation  between  hepatic 
abscess  and  a  suppurating  echinococcus  cyst  is  frequently  very  difficult. 
Neither  is  differentiation  between  a  cyst  and  a  Bofi  cancer  nodule  easy,  for 
such  nodules  may  frequently  produce  the  signs  of  fluctuation.  Confusion 
with  dropsy  of  the  gall-bladder  may  readily  be  avoided,  as  its  position  remote 
from  the  liver,  the  form  of  the  tumor,  and  the  anemia  will  point  out  the 
correct  diagnosis. 

Tbe  oval  form  of  hydronephrosis,  the  immobility  in  respiration,  its  posi- 
tion in  relation  to  the  colon,  palpation  in  tbe  knee-elbow  position,  and  an 
examination  of  the  urine  will  prevent  us  from  confounding  echinococcus  with 
hydronephrosis. 

Multilocular  echinococcus  also  frequently  exists  for  a  long  time  without 
symptoms,  and  tben  the  sensation  of  fulness  and  heaviness  in  the  epigastrium 
and  stubborn  jaundice  appear.  Bulging  in  the  hepatic  region  constantly  in- 
creases as  the  result  of  tbe  decided  enlargement  of  the  organ.  Palpation 
reveals  a  tumor  of  hard  consistence  like  cartilage;  the  surface  is  smooth  and 
nodulated.  Fluctuation  at  first  is  limited  to  individual  parts.  The  spleen 
is  usually  enlarged.  Nutrition  gradually  suffers;  ascites,  anasarca  and  at- 
tacks of  fever  occur.  Death  results  after  one  or  several  years,  accompanied 
by  the  symptoms  of  marasmus. 

In  form  and  size,  and  in  the  hardness  of  the  liver,  multilocular  echinococcus 
resembles  hepatic  cancer.  Bui  the  course  of  the  disease  is  slower,  and  nutritive 
disturbances  develop  only  in  the  advanced  stages.  Syphilis  of  the  liver  pre- 
Bents  other  forms  and  degrees  of  enlargement.  The  chills  and  marked  jaun- 
dice which  usually  occur  in  abscess  of  the  liver  will  differentiate  this  affection 
from  multilocular  echinococcus.  Hepatic  cirrhosis  ami  amyloid  liver  will,  as 
a  rule,  be  easily  differentiated  from  tbe  hydatid.  The  prognosis  has  usually 
been  considered  absolutely  unfavorable.  We  have  already  called  attention  to 
the  results  recently  obtained  by  operation. 

Echinococcus  of  the  pancreas  has  been  described  by  Subboitic,  Pericic  and 
Sal  is. 

Echinococcus  of  the  spleen  is  rare;  according  to  tbe  Pomeranian  staii>tics 
it  occurred  in  1  per  cent,  of  the  cases,  in  the  Mecklenburg  statistics  in  only 
1.96  pci-  cent.  The  parasite  finds  a  favorable  medium  for  it-  growth  in  the 
-i. ft  splenic  tissue.  In  the  main,  the  symptoms  of  Bplenic  echinococcus  resem- 
ble those  of  hepatic  echinococcus,  hut  with  the  difference  that  the  formation 
of  tumor  i-  only  upon  the  left  side.  Splenic  echinococcus  is  not  rarely  com- 
plicated by  echinococcua  of  other  organs. 

Echinococcus  <>}'  Ihr  kidney,  which  in  the  Mecklenburg  statistics  consti- 
tutes 3.5  per  cent,  «if  the  cases,  and  in  the  Pomeranian  L58  per  cent.,  usually 
develops  in  the  conical  substance.     Renal  echinococci   for  the  mosl   part  are 

unilateral.      Afl    it    gTOWB    all    part-    of    the    kidney    may    he    implicated    in    the 

disease,  and  the  kidney  he  transformed  into  a  large  echinococcua  cyst.     This 

cv-t  extend-  into  the  abd inal  cavity,  and  leadfi  to  dislocations  and  to  adhe- 
sion- to  neighboring  organs.  Diseases  of  the  mosi  varied  kind  may  thus 
he  simulated.  Small  tumor-  produce  no  symptoms;  larger  one-  cause  pressure 
phenomena,  difficulty  in  respiration,  etc.    After  year-  the  Bymptoma  of  maras- 


542  THE  ANIMAL  PARASITES  OF  MAN 

mus  develop,  provided  rupture  into  the  pelvis  of  the  kidney  and  discharge  of 
the  cysts  have  not  occurred.  The  urine  which  may  be  voided  prior  to,  with, 
or  after,  the  discharge  of  the  cyst  is  turbid,  occasionally  of  a  soapy-alkaline, 
milky,  or  turbid  appearance,  and  in  the  sediment  the  characteristic  contents  of 
the  cyst  are  found.  After  discharge  the  palpable  tumor  disappears,  to  recur 
after  some  time.  The  affection  may  last  for  many  years.  Occasionally  the 
echinococcus  takes  other  roads ;  perforation  into  the  pleural  cavity  and  abdom- 
inal cavity  has  repeatedly  been  observed. 

Eenal  echinococcus  differs  from  cysts  of  the  liver  and  of  the  spleen  by  the 
immobility  at  its  base,  by  its  outlines  which  may  be  determined  by  percussion 
from  the  borders  of  these  organs,  and  by  dislocation  of  the  colon.  The  differ- 
ential diagnosis  between  renal  echinococcus  and  hydronephrosis  is  very  diffi- 
cult. The  history  of  the  development  of  the  tumor,  the  proof  of  a  hindrance 
to  the  discharge  of  urine,  the  previous  presence  of  renal  calculi  or  of  a  stasis 
pyelitis,  point  to  the  presence  of  hydronephrosis. 

The  prognosis  of  renal  echinococci  is  considered  by  most  authors  to  be  very 
grave.  Fortunately,  with  the  advance  of  modern  surgery,  operative  treatment 
gives  better  results  than  formerly. 

In  the  adrenals  only  one  case  each  of  the  cystic  and  of  the  multilocular 
form  has  up  to  the  present  been  found. 

Echinococcus  of  the  urinary  bladder  has  been  reported  by  Hinsworth  and 
Schönfeld. 

Winterberg  has  described  a  case  of  echinococcus  of  the  prostate  gland. 

Echinococci  in  the  abdominal  cavity.  Primary  cysts  of  the  peritoneum 
appear  to  be  rare.  They  are  always  multiple.  Their  origin  may  be  referred 
to  a  profound  general  infection  or  to  an  autoinfection.  The  parasite  is 
usually  found  simultaneously  in  other  organs.  Numerous  adhesions  may  fre- 
quently preclude  the  determination  of  the  point  of  origin.  The  symptoms 
which  result  are  due  to  the  pressure  exerted  upon  the  abdominal  organs. 
Perforation  is  rare. 

Primary  retroperitoneal  echinococci  are  not  often  found  except  in  the 
connective  tissue  of  the  pelvis  and  in  the  female  genitalia,  where  the  cysts 
are  situated  subserously.  In  the  Pomeranian  statistics  we  find  only  one  case 
of  this  kind  described  by  Bitter.  Karewski  recently  published  two  cases.  The 
symptomatology  is  usually  obscure,  and  when  suppuration  takes  place  it  points 
to  a  perinephritic  abscess.  On  account  of  the  pressure  of  the  thick  layers  of 
muscles  and  of  the  bones  of  the  trunk,  held  by  tense  fascia,  the  echinococcus 
finds  but  little  room  for  growth,  and  is  forced  to  develop  from  the  surface 
by  daughter-  and  granddaughter-cysts  of  exogenous  growth.  Conspicuous 
symptoms  appear  only  when  suppuration  occurs.  To  facilitate  the  diagnosis, 
Karewski  advises  exploratory  puncture,  all  danger  being  obviated  by  the  extra- 
peritoneal position. 

Echinococci  of  the  mesentery  are  somewhat  infrequent,  and  their  diagnosis 
is  not  easy.  In  regard  to  their  differentiation  from  cysts  of  the  omentum, 
Hahn  states  that  the  latter  can  come  into  question  only  when  fixed  loops  of 
intestine  can  be  determined  between  the  tumor  and  the  abdominal  wall,  or  in 
the  surroundings  of  the  tumor,  or  in  the  limits  which  may  be  defined  by 


ECHINOCOCCUS  DISEASE  543 

palpation  or  by  adhesions.     If  the  intestine  is  in  front  the  tympanitic  note 
of  the  latter  is  the  most  important  diagnostic  symptom. 

Echinococcus  of  the  omentum  is  rarely  unilocular.  Cases  of  this  kind  have 
been  published  by  Grünig  and  Lütkemüller. 

Echinococcus  of  the  true  pelvis  and  of  the  genitalia.  In  the  male,  echino- 
cocci  in  the  true  pelvis  develop  in  the  space  between  the  rectum  and  the  blad- 
der. Their  growth  lead-  to  disturbances  of  function  of  the  rectum  and  bladder. 
Now  and  then  perforation  into  the  rectum  occurs. 

In  the  female  we  find  echinoeoccus  in  tin  uterus,  in  the  ovaries,  in  the 
ligamenta  lata,  in  the  anterior  and  posterior  halves  of  the  pelvis. 

Jn  the  nt'  ras  the  echinoeoccus  usually  develops  in  the  submucous  tissue. 
Scanzer's  view  that  the  embryo  in  its  wanderings  reaches  tin-  abdominal  open- 
in  Lr  of  the  Fallopian  tube  grasped  by  the  fimbriae,  enters  the  cavity  of  the 
uteru-.  and  develops  fully  there,  is  quite  properly  rejected  by  Schatz  for  the 
majority  of  cases.  The  submucous  seat  is  explained  by  Schatz  from  the  cir- 
cumstance that  the  embryo,  owing  to  greater  strength  of  the  blood  current 
in  that  direction,  particularly  at  the  time  of  menstruation,  is  forced  against 
the  interior  muscular  layer  near  the  mucosa.  It  evidently  develops  in  the 
muscles,  and  finally,  when  labor  pains  occur,  enters  the  cavity  of  the  uterus 
through  the  muscles  which  have  gradually  become  atrophic.  The  hydatid  has 
also  been  found  in  a  subserous  position. 

Th<-  echinoeoccus  lodged  in  the  wall  of  the  uterus  is  commonly  mistaken 
for  a  myoma,  if  echinococci  have  not  appeared  in  other  organs.  The  circum- 
stance that  the  wall  of  the  uterus,  which  in  the  case  of  myoma  is  usually 
decidedly  hypertrophied,  is  not  found  so  in  the  case  of  echinoc- 
(Schatz)  may  be  utilized  in  the  diagnosis.  Subserous  myomata  develop 
only  a  moderate  muscular  hypertrophy:  their  consistence  i>  n<>t  character- 
istic. Thirteen  cases  are  mentioned  in  literature  in  which  the  echinoco 
Bac  \\a-  an  impediment  at  birth  (Schmidt,  "  Oeber  Ech.  in  weibl.  Becken," 
I'  äs.  L893). 

Echinococci  of  the  ovaries  and  ligamenta  lata  are  rare.  Schnitze  could 
collect  from  literature  only  eleven  cases  of  echinoeoccus  of  the  ovary,  to  which 
he  added  two  cases  that  came  under  his  own  observation.  Schatz  remarks 
concerning  the  diagnosis  that  a  tumor  of  about  the  size  of  an  orange,  very 
deeply  seated  near  the  uterus,  should  cause  us  to  suspecl  echinoeoccus.  Later 
oup  of  such  tumors,  of  equal  >ize  and  closely  situated,  form-  an  important 
diagnostic  symptom.  Extrauterine  pregnancy  on  account  of  it-  rapid  prog 
ami  disease  of  the  tubes  on  account  of  the  characteristic  form  of  the  en!. 
ment,  can  scarcely  be  confounded  with  echinoeoccus.  Beowit  recently  -aw 
both  tubes  transformed  into  echinoeoccus  Bacs. 

Echinococcus  of  the  cellular  tissue  of  ihr  pelvis  is  in  the  majority  of 
found  upon  the  inner  surface  of  the  posterior  wall,  less  frequently  upon  the 
anterior.  The  diagnosis  is  greatly  facilitated  by  the  ease  with  which  the 
diseased  area  may  be  reached.  Echinococcus  of  the  pelvis  may  be  Busp 
if  one  or  several  Bmooth,  tense,  elastic  but  slightly  movable  tumors,  not  painful 
upon  pressure,  are  found,  ami  the  ovaries  may  be  distinctly  determined.  In 
main  cases  the  cyst  i-  situated  between  the  uterus  and  the  rectum.     I 


544  THE  ANIMAL  PARASITES  OF  MAN 

and  cachexia  are  absent.  The  simultaneous  presence  of  the  parasite  in  other 
organs  facilitates  the  diagnosis. 

Echinococci  of  the  scrotum,,  the  epididymis  and  the  tunica  vaginalis  have 
been  observed  in  a  few  cases. 

Echinococcus  of  the  bones  is  rare.  In  the  Pomeranian  statistics  not  a 
single  case  is  mentioned. 

The  parasite  is  found  more  frequently  in  the  long  bones  than  in  the 
short  bones.  In  the  cases  collected  by  Poppe,  the  frequency  with  which  differ- 
ent bones  were  affected  was  as  follows :  Humerus  23  per  cent.,  pelvis  and  tibia 
18  per  cent.,  vertebral  column  and  femur  13  per  cent.,  frontal  bone  5  per  cent., 
sphenoidal  bone,  scapula,  index  finger,  sternum,  and  ribs  each  1  case. 

The  parasite  develops  in  the  medullary  cavity,  i.  e.,  in  the  spongy  sub- 
stance, and  is  at  first  entirely  latent.  Only  with  increasing  growth  do  char- 
acteristic changes  occur.  In  the  long  tubular  bones  the  medullary  cavity 
dilates,  the  wall  of  the  bones  becomes  eroded,  the  external  wall  thin.  Often 
there  is  severe  pain.  Slight  trauma  leads  to  spontaneous  fracture  without 
any  previous  symptom  of  disease  of  the  bone.  The  fracture  does  not  heal,  a 
fact  which  usually  enables  us  to  recognize  the  nature  of  the  affection.  Schnitz- 
ler's  case  proves  that  occasionally,  even  in  echinococcus  of  the  long  tubular 
bones,  decided  changes  in  form  and  circumference  of  the  bones  may  take 
place. 

NEMATODA,  THREAD-WORMS 

The  nematoda  are  slender,  cylindrical,  curved,  thread-like  or  tubular 
worms.  Their  surface  is  smooth  and  curled,  occasionally  supplied  with  hook- 
lets,  hairs,  or  bristlets.  The  anterior  end  of  the  body  in  which  the  mouth 
cavity  is  situated  is  somewhat  slender,  the  posterior  end  is  pointed  or  rounded. 
The  anus  is  usually  found  upon  the  ventral  surface.  The  nematoda,  at  least 
those  which  are  parasitic  in  man,  are  of  different  sexes.  The  males,  as  a 
rule,  are  shorter  and  more  slender  than  the  females.  In  the  males  the  posterior 
end  of  the  trunk  is  usually  curved,  while  in  the  female  it  shows  a  straight 
elongation.  In  the  male  the  sexual  opening  and  the  anus  are  one,  while 
in  the  female  the  former  is  usually  found  at  about  the  center  of  the  body. 
Of  the  nematoda  which  are  parasitic  in  man  I  shall  briefly  mention : 

Rhabditis  terricolas,  Dujardin,  1815,  which  was  once  found  in  the  cadaver. 

Bhabditis  pellio,  Schneider,  1866,  was  found  in  acid  urine  containing  albu- 
min, blood  and  pus.     I  believe  that  I  once  saw  this  parasite  with  Westphal. 

Rhabditis  Nfiellyi,  Blanchard,  1885,  in  a  cabin  boy  produced  an  itching 
skin  eruption. 

Anguillula  putrefaciens.  Kühn,  1879,  was  once  observed  in  vomitus.  The 
parasite  was  evidently  taken  into  the  stomach  of  the  affected  individual  with 
onions,  and  then  had  produced  vomiting. 

Of  decidedly  greater  interest  is: 

Anguillula  intestinalis  et  stercoralis,  Bavay,  1877. 

In  1876  Normand,  a  French  marine  surgeon,  found,  in  the  feces  of  a 
soldier  who  suffered  from  the  so-called  Cochin-China  diarrhea,  anguillula  which 


NEMATODA,  THREAD-WORMS  545 

were  designated  by  Bavay  as  anguillula  stercoralis.  Another  parasite  soon 
afterward  found  by  Normand  in  patients  of  this  kind  was  described  by  Bavay 
as  anguillula  intestinalis.  By  the  Investigations  of  Leuckart,  Grassi,  and 
Leichtenstern,  the  relations  of  these  parasites  have  been  determined  with  cer- 
tainty. For  purposes  of  study,  I  may  refer  to  the  investigations  of  the 
previously  mentioned  authors  as  well  as  to  those  of  Askanazy  and  Zinn. 

According  to  these  investigations  the  development  occurs  in  the  following 
manner:  the  hermaphroditic  mother  animal  of  the  anguillula  intestinalis. 
according  to  Askanazy.  lodges  in  the  intestinal  wall,  chiefly  in  the  mucous 
membrane,  and  frequently  bores  its  way  into  the  epithelium  of  the  gland. 
there  to  take  up  nutritive  products.  The  females  at  the  same  time  deposil 
their  eggs  here.  The  ova  are  transformed  into  embryos  which  then  enter 
the  intestinal  cavity.  These  are  met  with  in  fresh  feces,  often  in  great  num- 
bers, and.  according  to  Zinn,  in  aboul  twelve  hours  are  transformed  into  filaria- 
likc  larv;e.  These  again  enter  the  intestinal  canal  of  man,  and  are  here 
formed  into  parasitic  anguillula.    This  process  is  called  direct  metamorphosis. 

Other  embryos  of  anguillula  intestinalis  develop  outside  the  body  in  about 
two  to  three  days  into  sexually  ripe  male  and  female  animals  (rhabditis  ster- 
coralis). The  direct  descendants  of  these  are  the  embryos  of  the  rhabditis 
stercoralis.  from  which  the  filaria-like  larva'  are  again  formed.  The  latter 
wander  into  the  intestinal  canal  of  man.  and  grow  into  mother  animal-  of  the 
parasitic  anguillula  intestinalis.  This  mode  of  development  is  designated  by 
Leuckart  as  heterogeny.  This  heterogeny,  as  was  lir-t  emphasized  by  Leich- 
tcmtcni.  doe-  not  occur  in  the  majority  of  cases,  particularly  in  those  of 
European  origin. 

Anguilluliasis  occurs  not  only  in  southeastern  Asia,  Martinique  and  Bra- 
zil, hut  was  met  with  in  1878  and  1879  by  Grassi  and  Parona  in  Italy,  simul- 
taneously with  anchylostomiasis.  Lately  Askanazy  found  them  in  a  game- 
keeper in  Easl  Prussia  who  had  never  left  his  home,  and  who  never  came 
in  contact  with  Rhenish  brickmakers. 

The  parasites  live  in  the  juices  of  the  small  intestines.  Askanazy  also 
found  them  in  the  tissues  of  the  mucosa,  sometimes  Btretched  out  or  rolled 
together.  They  distribute  themselves  in  the  muscularis  mucosa,  and  are  me\ 
with  in  greal  numbers  in  the  region  of  Lieberkiihn's  glands.  The  parasite 
enters  the  wall-  of  the  intestines  to  partake  of  the  chyle.  Here,  according 
to  Askanazy,  the  eggs  are  deposited,  and  the  parasite  goes  through  it-  b! 
of  development.  Teissier  ha-  observed  that  the  embryos  occasionally  enter  the 
circulation,  Askanazy  Beems  to  Favor  the  view  that  the  parasites  are  to  he 
regarded  a-  no  more  than  simple  commensals. 

( »f  special  interest  i-  the : 

Filaria  medinensis  Velsch,  1674. 

The  females  attain  a  length  of  from  60  to  80  cm.  and  in  form  and  appear- 
ance resemble  a  catgui  -trim:.  The  male,  according  to  Charles,  ha-  also 
recently  been  found.  It  is  only  I  cm.  in  length.  Dracontiasis,  a-  the  path- 
ologic phenomena  produced  by  the  parasite  were  called  by  Galen,  is  due  to 
the  fact  that  the  worm  penetrates  the  human  organism,  an. I  may  remain  for 
;;.; 


546  THE  ANIMAL  PARASITES  OF  MAN 

a  long  time  under  the  skin  of  the  connective  tissue  entirely  latent.  Only  after 
completing  its  full  growth — the  period  of  incubation  appears  to  be  from  eight 
to  ten  months — does  it  leave  the  papillary  bodies  of  the  corium  by  the  forma- 
tion of  an  abscess. 

The  medina  worm  is  most  frequently  found  in  tropical  countries,  particu- 
larly in  the  Old  World :  in  Arabia,  around  the  Persian  Gulf,  upon  the  Ganges, 
the  Caspian  Sea,  in  Upper  Egypt,  Abyssinia  and  Guinea.  It  has  also  been 
carried  to  South  America. 

The  filaria  embryos  enclosed  in  the  uterus  can  only  secure  their  freedom 
by  rupture  of  the  mother  animal.  How  their  further  dissemination  in  the 
human  organism  takes  place  has  not  yet  been  definitely  determined.  It  has 
been  thought  that  the  embryo  finds  ingress  through  the  skin.  Some  authors 
assume  that  infection  is  conveyed  by  drinking-water.  Probably  the  worm 
finds  a  hold  around  the  lower  extremities,  especially  about  the  malleoli.  It  is 
much  more  rarely  found  upon  the  upper  parts  of  the  body. 

The  symptoms  resemble  the  formation  of  a  furuncle,  at  the  base  of  which 
the  parasite  is  seen.  Upon  extraction  of  the  worm,  rupture  of  the  parasite 
should  be  avoided,  and  care  should  be  taken  to  leave  no  fragments  behind, 
for,  otherwise,  decided  inflammation  soon  appears. 

A  more  delicate  and  smaller  parasite  is : 

Filaria  loa  Guyot,  1778, 

which  lodges  between  the  conjunctiva  and  bulbus  oculi,  and  gives  rise  to  abscess 
formation  in  this  region.  The  paraske  is  found  chiefly  in  negroes  upon  the 
west  coast  of  Africa,  also  in  South  America  and  in  the  Antilles. 

The  other  filariae  are  not  of  special  interest.  Among  these  I  may  mention 
the  filaria  lentis,  Diesing,  1851,  the  filaria  hominis  bronchialis,  Kudolphi,  1819, 
the  filaria  labialis,  Pane,  1861,  the  filaria  inermis,  Grassi,  1887,  the  filaria 
immitis,  Leidy,  1856,  the  filaria  rectiformis,  Leidy,  1880,  the  filaria  hominis 
oris,  Leidy,  1850,  the  strongylus  subtilis,  Loos,  1895,  and  the  filaria  volvulus, 
Leuckart,  1893. 

Filaria  Bancrofti,  Cobbold,  1887. 

The  embryos  of  this  parasite  were  found  in  the  fluid  of  a  lrydrocele  by 
Demarquay  in  1863  in  a  Havanese.  They  were  found  later  in  the  blood, 
the  urine,  and  in  the  chyle  in  so-called  lymph-scrotum  and  in  elephantiasis. 
Bancroft  and  Lewis  found  the  mature  sexual  forms  in  the  lymph-vessels.  The 
females  bear  living  young,  which  enter  the  blood  with  the  lymph-stream.  Ac- 
cording to  Manson  they  enter  the  blood  only  after  sunset;  after  midnight 
their  number  again  decreases.  If  the  patient  sleep  during  the  day,  the  em- 
bryos appear  in  the  blood  during  the  daytime. 

This  periodic  appearance  is  explained  by  v.  Linstow  by  the  circumstance 
that  the  peripheral  cutaneous  vessels  dilate  during  sleep,  and  thereby  permit 
the  entrance  of  the  embryos,  which  otherwise  would  only  be  present  in  the 
larger  vessels.  Manson  states  that  the  appearance  of  the  embryos  is  simul- 
taneous with  the  swarming  of  mosquitoes,  which  suck  the  blood  of  the  affected 
person,  and  are  then  filled  with  embryos.    A  part  of  the  young  brood  develop 


XEMATODA,  THREAD-WORMS 


547 


with  the  mosquitoes,  and  a  part  are  destroyed.  The  female  mosquitoes  die 
after  depositing  their  eggs  in  water.  But  the  mature  filaria,  meanwhile,  have 
acquired  the  power  of  living  for  a  time  in  water.  With  the  water  they  enter 
the  human  host  and  there,  chiefly  in  the  lymph-vessel  system,  they  become 
sexually  mature  animals. 

The  male  parasite  is  about  83  mm.  in  length,  and  has  the  thickness  of  a 
hair  of  the  head,  while  the  female  is  155  mm.  in  length  and  0.7  mm.  in 


Fig.  53. — Filaria  Embryos. 
This  preparation  I  owe  to  the  kindness  of  Professor  -Magathäes  of  Rio  de  Janeiro. 

breadth.  The  posterior  end  of  the  male  is  pointed,  and  rolled  in  a  spiral. 
The  sexual  opening  of  the  female  is  close  to  the  bend.  In  fresh  blood  the 
embryo  shows  active  movements  of  both  end-:  it  is  perfectly  transparent,  and 
only  in  the  middle  of  a  parasite  may  a  few  granule  clumps  be  recognized. 
Scheube  found  them  upon  the  average  0.216  mm.  long  and  0.004  nun.  broad. 
The  home  of  the  filaria  is  tropical  Asia,  Africa,  America,  and  Australia. 

Besides  the  filaria?  of  Bancroft  and  Cobbold,  otheT  blood  filarial  are  also 
found.  The  filaria  Magathäesi  must  first  be  mentioned.  It  is  decidedly  larger 
than  those  previously  named,  and  in  Brazil  lives  in  the  heart  of  man.  fur- 
thermore. Man-on  has  described  the  filaria  sanguinis  hominis  major — tin1 
filaria  diurna,  Man-on  ;  the  filaria  sanguinis  minor — the  filiaria  perstans,  Man- 
son;  the  filaria,  Demarquayi;  the  filaria,  Ozzardi.  The  sexually  ripe  form  has 
qoI  yel  been  found,  and  v.  Linstow  believes  these  filaria  to  lie  developmental 
phases  of  one  and  the  same  embryonic  larval  form. 

The   filaria   produce  marked   Bymptoms  in    the  lymphatic   -v-tem.  the  walls 

of  which  -how  inflammatory  changes.  Thrombosis  and  cicatricial  closure  of 
tin'  lymphatic-  cause  varicose  dilatation  of  the  peripheral  vessels  and  the  forma- 
tion of  lymph-cysts.  These  rupture  and  their  contents  are  sei  free  in  the 
urinary  bladder,  under  the  cutis,  or  in  other  tissues.  The  perilymphatic  con- 
nective i i  —  in-  i-  also  inflamed,  finally  Bymptoms  are  produced  which  resem- 
ble ele|»hantia-i-. 


548  THE  ANIMAL  PARASITES   OF  MAN 

The  filaria  embryos  appear  to  circulate  for  a  long  time  in  the  blood  before 
they  produce  symptoms.  Gradually  general  malaise  develops,  also  pain  in  the 
small  of  the  back  and  renal  region,  and  in  the  scrotum,  followed  by  an  inter- 
mittent hematochyluria.  Fever  and  enlargement  of  the  spleen  often  accom- 
pany the  symptoms.  After  continuing  for  days  and  weeks  these  phenomena 
cease,  to  reappear  at  the  end  of  a  certain  period.  During  the  attack  the  urine 
is  of  a  peach-red  color.  Blood  and  blood  coaguli  are  found  in  the  sediment, 
while  the  urine  above  this  is  turbid,  whitish,  and  has  a  tint  of  yellow  not 
unlike  diluted  cream.  Upon  the  surface  a  cream-like  fatty  layer  may  fre- 
quently be  noticed.  Sugar  and  peptone  are  absent;  Cholesterin,  lecithin, 
neutral  fats,  and  fatty  acids  are  present.  Besides  the  embryos,  red  and  white 
corpuscles  and  large  and  small  fat  globules  are  found.  Gradually  the  lymph- 
glands  enlarge,  in  the  males  the  scrotum,  in  the  female  the  labia.  The  symp- 
toms disappear,  to  return  in  a  short  time  in  an  exaggerated  form.  Elephan- 
tiasis-like swellings  form  upon  the  lower,  and  later  upon  the  upper,  extremities. 
The  disease  finally  causes  death,  after  running  a  course  for  years  with  the 
symptoms  of  marasmus. 

Whether  recovery,  which  occasionally  is  spontaneous,  is  due  to  remedies 
or  not  is  very  questionable.  Drugs  appear  to  have  no  influence  upon  the  para- 
site. Surgical  interference  has  been  frequently  attempted,  but,  according  to 
Seheube,  does  not  prevent  relapses.  The  utmost  stress  is  to  be  laid  upon 
prophylaxis,  and  in  this  the  question  of  drinking-water  is  of  special  impor- 
tance. The  habit  of  drinking  unfiltered  water  from  ditches  and  cisterns  in 
the  tropics  is  undoubtedly  a  cause  of  the  distribution  of  the  parasite.  Physi- 
cians living  in  these  regions  strenuously  advise  that  only  filtered  water,  or 
drinking-water  from  closed  conduits,  be  used. 

It  is  evident  that  our  knowledge  of  filariasis  is  far  from  complete,  and  it 
is  hoped  that  future  investigations  may  shed  light  upon  some  of  its  dark  prob- 
lems. For  example,  John  O'Neill  observed  a  filaria  which  produced  prurigi- 
nous  vesicles  and  nodules  upon  the  fingers  and  elbows  with  severe  itching,  and 
of  this  parasite  nothing  further  has  been  heard. 

Among  the  most  frequent  human  parasites  are  the  ascaris  lumbricoides, 
Linne,  1758,  trichocephalus  dispar,  Budolphi,  1801,  and  the  oxyuris  vermicu- 
laris,  Linne,  1767. 

A  zoologic  description  of  these  parasites  is  unnecessary  as  they  are  well 
known. 

The  ascaris  lumbricoides  resembles  the  rain-worm,  and  is  unquestionably 
the  most  common  parasite  of  man.  Its  embryology  was  first  clearly  described 
by  Grassi  in  the  year  1887,  and  he  proved  that  it  does  not  require  an  inter- 
mediary host.  The  fact  of  direct  infection  with  embryo-containing  ova  has 
been  confirmed  by  the  further  investigations  of  Lutz  and  Epstein. 

Besides  the  ascaris  lumbricoides,  the  ascaris  mystax,  Zeder  (the  nematode 
of  the  cat  or  dog),  has  also  been  occasionally  found  in  man.  This  parasite 
is  much  smaller  than  that  of  man  ;  and  upon  the  end  containing  the  head 
two  wing-like  processes  are  situated  which  at  once  distinguish  this  worm  from 
those  mentioned  above. 


NEMATODA,  THREAD-WORMS  549 

Ascaris  maritima,  Leuckart,  1876,  has  up  to  this  time  been  found  only 
once — in  Greenland. 

Wherever  ascarides  hosts,  including  swine  and  cattle,  distribute  the  ova  in 
the  vicinity  of  human  habitations,  man,  whose  habits  and  customs  bring  him 
into  close  contact  with  the  foci  of  infection,  acquires  the  ova  of  the  nema- 
tode. The  agricultural  population,  in  particular,  by  their  occupation,  and, 
above  all,  the  children,  by  playing  in  the  infected  earth  take  up  the  embryo. 
Children  in  cities  are  much  more  rarely  contaminated.  By  the  slaughter  of 
pigs  and  cattle  at  home  or  in  the  immediate  vicinity,  the  infectious  germs  are 
widely  distributed  about  the  house  and  in  the  garden,  which  is  the  ordinary 
playground  of  the  children.  In  the  first  and  second  years  children  are  much 
more  rarely  attacked  than  in  the  third  year  and  upward.  In  later  life  ascarides 
are  more  rarely  met  with  but  no  age  is  exempt.  Often  infection  occurs 
through  drinking-water  or  food,  such  as  fruit,  vegetables,  and  the  like. 

The  usual  seat  of  the  parasite  is  the  small  intestine.  A  single  parasite  is 
rarely  found  ;  usually  they  collect  in  numbers. 

The  parasites  frequently  produce  no  symptoms,  and  their  accidental  dis- 
charge  betrays  their  presence.  When  the  parasites  are  numerous,  they  pro- 
duce more  or  less  decided  disturbance.  In  the  milder  cases  only  gastric  symp- 
toms appear:  Anorexia,  nausea,  salivation,  irregular  bowel  action.  In  children 
there  is  frequently  a  slightly  swollen  appearance,  deeply  sunken  eyes,  itching 
of  the  nose,  nocturnal  grinding  of  the  teeth.  Various  nervous  symptoms,  such 
as  convulsions,  epileptiform  attack-,  headache,  pain  in  the  back  of  the  neck. 
etc.,  may  occur,  although  these  are  less  frequent.  Demme  saw  cases  of  severe 
anemia  due  to  the  presence  of  numerous  nematodes;  Baelz  also  believes  that 
ascaris  may  occasionally  produce  severe  anemia.  Leichtenstern  saw  severe 
anemia,  and  in  another  case  larval  malaria  with  enlargement  of  the  spleen, 
improve  niter  expulsion  of  the  ascarides.  These,  as  well  as  many  other  obser- 
vations, do  not  permit  us  to  regard  this  nematode  as  the  harmless  guest  which 
it  is  usually  assumed  to  be.  The  severe  nervous  symptoms  have,  for  the  mosi 
part,  been  looked  upon  a-  reflex.  The  observations  of  Euber,  \.  bin-tow-  and 
others  have  shown  that  this  nematode  contain-  a  poisoD  which  may  give  rise 
to  urticaria  and  conjunctivitis.  It  has  a  sharp  odor,  manifest  even  on  handling 
of  the  parasite.  As  I  have  explained  elsewhere  it  is  quite  possible  to  look 
upon  the  nervous  Bymptoms  which  accompany  infection  by  nematode-  not  as 
reflex  bul  as  toxic. 

Decided  local  disturbances  may  also  appear  when  numerous  ascarides  are 

present.  Sometime-,  rarely  it  is  true,  the  worm-  may  form  a  hall  so  that  the 
Bymptoms  of  intestinal  occlusion  may  arise.  Leichtenstern  questions  ibis, 
bul  from  the  observations  of  Mosler,  Pelczynski,  Stepp.  Sperling  and  other-, 
it  may  be  considered  as  proven.  The  view  that  nematodes  may  perforate  the 
intact  mucous  membrane  has  not  yet  been  positively  demonstrated  by  investi- 
gation, but  if  ulcer  formation  is  present  it  is  quite  possible  that  the  parasites 
may  perforate  the  ulcerated  surface. 

It  i-  a  remarkable  fact  that  at  certain  times,  especially  in  Berious  febrile 
diseases,  ascarides  leave  their  usual  Beat,  the  -mall  intestine,  and  begin  to  wan- 
der.    Either  they  enter  the  large  intestine,  are  voided  from  tin-  independently, 


550  THE  ANIMAL  PARASITES  OF  MAN 

and  are  later  found  rolled  up  in  the  bed,  or  they  are  voided  with  the  fecal 
masses.  In  other  cases  they  enter  the  stomach,  thence  the  esophagus,  and  find 
their  exit  by  means  of  the  mouth  and  nose.  If  they  effect  an  entrance  into 
the  larynx,  severe  suffocative  phenomena  are  produced  which  may  cause  death. 
Not  rarely  they  find  ingress  to  the  excretory  ducts  of  the  large  abdominal 
glands,  particularly  the  common  gall  duct,  and  thence  reach  the  gall-bladder 
or  the  liver  and  here  produce  serious  lesions.  More  rarely  they  invade  the 
pancreatic  duct  or  the  vermiform  appendix.  The  tendency  of  ascarides  to 
lodge  in  preformed  foramina  explains  their  occurrence  in  the  abdominal  cavity 
after  perforation  of  the  intestine.  If  nematodes  are  capable  of  thus  penetrat- 
ing into  intra-  or  extra-peritoneal  abscesses,  in  their  further  course  they  may 
be  found  in  very  remote  situations.  Thus,  nematodes  have  been  discharged 
from  the  bladder,  from  the  uterus,  and  from  abscesses  of  the  abdominal  cavity. 

If  there  is  a  suspicion  of  helminthiasis,  the  microscopical  investigation  of 
the  feces  and  the  finding  of  the  characteristic  ova  will,  as  a  rule,  enable  us  to 
make  a  positive  diagnosis. 

The  prognosis  is  generally  favorable ;  only  exceptionally,  by  the  wandering 
of  the  parasites,  are  threatening  symptoms  produced. 

The  administration  of  santonin  will  generally  lead  to  the  expulsion  of  the 
parasite.  This  drug  should  never  be  given  upon  an  empty  stomach,  however, 
as  rapid  absorption  permits  its  toxic  properties  to  appear  before  its  anthel- 
mintic. As  is  well  known,  the  symptoms  of  santonin  poisoning  consist  of 
yellow  sight,  yellow  discoloration  of  the  urine,  general  malaise,  vomiting  and 
spasms,  which  may  readily  become  dangerous  in  delicate  children.  Laxatives 
soon  cause  the  discharge  of  the  poison. 

Santonin  is  given  to  children  in  doses  of  0.025-0.05,  to  adults  in  doses 
of  0.1.  Lozenges  which  usually  contain  0.025-0.05  of  santonin  may  be  ob- 
tained in  pharmacies,  and  one  of  these  should  be  taken  two  or  three  times 
daily.  Upon  the  third  day  a  laxative  is  administered,  and  frequently  the 
worms,  which  have  been  only  stupefied,  are  discharged. 

The  oxyuris  vermicularis,  Linne,  1767,  is  also  a  parasite  that  is  well  known. 
The  direct  development  of  the  oxyuris  without  intermediary  host,  which  was 
indicated  by  the  investigations  of  Leuckart,  is  generally  accepted.  By  the 
swallowing  of  oxyuric  ova,  Leuckart,  Grassi  and  others  have  directly  infected 
themselves. 

It  does  not  appear  to  me  to  be  sufficiently  recognized  that  the  ova  are  not 
deposited  in  the  intestine  of  man,  but  that  the  mature  females  leave  the  intes- 
tine independently  or  with  the  feces.  We  can  never  conclude  from  the  absence 
of  oxyuris  ova  in  the  feces  that  this  parasite  is  not  present  in  the  intestine.  Only 
outside  of  the  intestinal  canal  does  the  female  discharge  its  ova  in  the  fecal 
masses.  Frequently  the  surroundings  of  the  anus  are  thickly  covered  with  oxy- 
uris ova  which  have  been  deposited  there  by  female  parasites  which  have  been  in- 
dependently discharged.  Tn  the  ova  an  embryo  soon  develops  which,  however, 
does  not  extrude  from  its  sac  until  after  retransportation  to  the  human  intes- 
tinal tract,  Unpared  fruit,  fresh  vegetables,  berries  and  other  fruits  which 
have  come  into  the  slightest  contact  with  infected  feces  often  bring  about  this 
infection.     In  other  cases  transmission  is  brought  about  by  clothing  which  is 


NEMATODA,  THREAD-WORMS  551 

used  in  common,  or  by  various  utensils  which  may  be  contaminated  with  ova. 
Ova  have  been  repeatedly  found  in  the  dirt  of  the  finger  nails  of  oxyuris  hosts. 
This  observation  sufficiently  explains  why  oxyuris  hosts  are  rarely  found  iso- 
lated  in  families,  pensions,  etc.,  and  the  same  finding  also  explains  the  well- 
known  tenacity  of  the  affection,  which  has  been  known  to  physicians  for  a 
Long  time.  The  oxyuris  host  evidently  infects  himself  anew  almost  daily,  or 
even  every  night. 

The  embryos  which  have  been  set  free  in  the  stomach  develop  to  sexual 
maturity  in  the  small  intestine.  The  impregnated  females  enter  the  cecum, 
and  there  await  the  time  for  depositing  their  ova.  When  this  period  has 
arrived,  they  wander  toward  the  rectum,  of  beyond  this,  and  are  discharged. 

No  age  is  exempt  from  the  parasite,  but  it  is  particularly  frequent  in 
children.  Great  uncleanliness,  huddling  together,  and  sleeping  with  infected 
persons  favor  contagion.  The  expulsion  of  parasites  is  so  constant  because  of 
their  rapid  increase  that  opportunity  for  the  entrance  of  new  ova  may  be  Long 
delayed,  and  it  is,  therefore,  not  rare  for  persons  to  harbor  a  parasite  for  a 
great  many  years. 

If  the  number  of  parasites  is  small,  they  betray  their  presence  only  now 
and  then  by  Itching  and  burning  in  the  rectum.  In  sensitive  individuals,  after 
passing  through  the  anus,  a  few  parasites  only  may  cause  a  number  of  symp- 
toms. These  disturbances  are  decidedly  increased  by  the  presence  of  consid- 
erable numbers  of  the  oxyuris.  By  their  serpentine  movements  in  the  lower 
portion  of  the  intestine  they  produce  intense  itching  in  the  anus.  This  is  par- 
ticularly marked  as  soon  as  the  patients  go  to  bed.  Sleep  is  prevented  or  is 
interrupted.  The  periodicity  of  these  symptoms  is  conspicuous,  and  as  yet 
no  sufficient  cause  for  this  has  been  assigned.     Large  numbers  of  oxyuris  cause 

marked  catarrhal  irritation  of  the  intestinal  1 sous  membrane,  perhaps  also 

erosions,  which  are  brought  about  by  the  active  boring  movements  of  the  head 
extremity  of  the  animals.  The  venous  vessels  dilate  as  in  the  case  of  hemor- 
rhoids. Frequently  oxyuriasis  is  complicated  with  hemorrhoidal  conditions 
and  chronic  catarrh  of  the  rectum.  In  consequence  of  this  the  bowel-  not 
rarely  become  irregular  and  diarrheic,  and  the  symptoms  of  tenesmus  appear. 
A  number  of  consensual  symptoms  may  also  develop,  which  in  children  readily 
lead  to  onanism.  Oxyuris  may  cause  pruritus;  in  the  vagina  in  girls  a  leukor- 
rhea.  in  the  prepuce  in  boys  a  balanitis.  Marro  found  in  a  pus  cyst  well-pre- 
served ova  of  oxyuris  vermicularis. 

Reflex  symptoms  of  the  most  varied  kind-,  due  to  oxyuris,  are  said  to  occur 
with  particular  frequency  in  neuropathically  predisposed  individuals;  I  have 
gathered  a  number  of  observations  of  this  kind.  At  all  events,  the  presence 
of  numerous  parasites  is  not  without  an  influence  on  the  affected  organism. 
In  feeble  persons,  particularly  in  children,  we  note  that  the  nutrition  Buffers, 
the  patient  becomes  weak  and  anemic,  and  there  i-  b>--  of  weight.  After 
expulsion  of  the  parasite,  however,  the  entire  condition  of  the  carrier  often 
improves  suddenly.  Occasionally  the  oxyuris  wander-  Into  the  stomach,  from 
here  to  the  esophagus,  to  the  mouth  or  to  the  nose.  Hartmann  saw  the  fre- 
quenj  expulsion  of  oxyuris  from  the  nose.     It  was  accompanied  by  the  most 

ere  irritative  symptoms,  epileptiform  attack-,  and  psychical  disturbances. 


552  THE   ANIMAL  PARASITES  OF  MAN 

These  were  actually  produced  by  the  parasite,  for  after  its  destruction  by  in- 
jections into  the  nose  of  corrosive  sublimate  solution  and  the  internal  admin- 
istration of  antipyrin,  these  nervous  symptoms  at  once  disappeared. 

The  diagnosis  where  oxyuriasis  is  suspected  depends  upon  investigation  of 
the  feces,  or  examination  of  the  anus  and  its  surroundings.  If  the  finding 
is  negative,  the  patient  is  told  to  use  a  small  enema  of  cold  water  immediately 
upon  the  appearance  of  the  symptoms.  In  the  return  flow  of  the  water,  the 
parasites,  if  present,  will  be  readily  recognized.  The  microscopic  examination 
of  the  soiled  parts  around  the  anus  readily  reveals  eggs  if  present.  Ova  are 
found  in  the  feces  only  if  simultaneously  also  the  macroscopically  recognizable 
female  oxyuris  is  present. 

The  removal  of  oxyuriasis  often  requires  great  patience.  In  the  first 
place  it  is  necessary  to  prevent  the  importation  of  ova  by  all  tendencies  and 
habits  which  favor  this.  The  sleeping  together  of  well  and  sick  children,  the 
common  use  of  clothing,  sponges,  towels  is  to  be  prohibited.  Frequent 
change  of  bedding  and  cleanliness  of  the  finger  nails,  etc.,  are  to  be  advised. 
Moreover,  the  parasites  which  are  present  in  the  small  intestine,  and  particularly 
in  the  cecum,  must  be  expelled  by  purgatives,  such  as  castor  oil,  rhubarb,  com- 
pound infusion  of  senna,  etc.  At  the  same  time  I  employ  santonin.  But  the 
simultaneous  employment  of  intestinal  infusions  is  absolutely  necessary  in 
order  to  expel  the  oxyuris  which  have  entered  the  large  intestine.  In  severe 
cases  I  add  to  the  water  one  to  two  teaspoonfuls  of  chlorin  water,  vinegar, 
0.2  to  1  per  cent,  of  medicated  soap.  As  a  common  household  remedy  garlic 
is  also  employed. 

Among  the  most  frequent  and  also,  as  a  rule,  most  harmless  intestinal  para- 
sites is  the 

Trichocephalus  dispar,  Rudolphi,  1801. 

This  organism  is  well  known,  and  therefore  a  zoologic  description  is  un- 
necessary. 

The  parasite  does  nor  require  an  intermediary  host.  We  have  little  knowl- 
edge of  the  method  by  which  it  enters  the  human  intestinal  tract.  Its  long 
period  of  development  and  the  great  resistance  of  the  ova  to  external  influ- 
ences evidently  favor  the  invasion.  Dried  and  pulverized  to  dust,  they  are 
readily  consumed  with  raw  fruit,  vegetables  or  drinking-water,  and  thus  enter 
the  human  organism.  After  the  young  embryos  have  left  the  membrane  of  the 
ovum,  they  attain  their  development  in  the  small  intestine,  and  finally  lodge 
in  the  cecum.  The  parasite  is  usually  found  in  but  few  specimens.  If  found 
numerously  the  signs  of  chronic  catarrh  may  develop  in  that  part  of  the  intes- 
tinal tract  which  they  inhabit.  The  parasite  adheres  to  the  mucous  mem- 
brane in  such  a  way  that  the  anterior  end  of  the  head,  which  is  curled  in  sev- 
eral folds,  surrounds  the  individual  parts  of  the  mucous  membrane.  In  other 
cases  it  has  been  proven  that  the  entire  anterior  thin  portion  of  the  body — more 
than  two-thirds  of  the  worm — penetrates  the  surface  of  the  intestinal  mucous 
membrane.  Accordingly  it  is  often  very  difficult  to  loosen  the  parasite  from 
its  hold  in  the  mucous  membrane. 

In  regard  to  the  symptoms,  in  general  little  is  known.     In  many  cases, 


XEMATODA,  THREAD-WORMS  553 

perhaps  in  the  majority,  there  are  apparently  no  symptoms.  Only  when  a 
massive  collection  becomes  lodged  in  the  cecum  or  in  the  colon,  local  difficulty 
may  result  from  the  irritation  which  the  worms  produce  by  boring  their  way 
deep  into  the  mucous  membrane.  Moosbrugger,  Burchard,  Federolf  have  seen 
severe  symptoms  due  to  trichocephales :  Extreme  anemia,  enteritis  with  pro- 
fuse hemorrhagic  stools,  emaciation  and  loss  of  strength.  Since  Askanazy  has 
shown  that  the  trichocephalus  invariably  has  an  iron-containing  pigment  in 
its  intestinal  epithelium,  the  origin  of  which  is  the  hemoglobin  of  the  blood, 
this  form  of  helminthiasis  will  evoke  much  greater  intere-t. 

The  diagnosis  may  readily  be  made  by  the  microscopic  demonstration  of  the 
characteristic  ova,  thick-shelled  brown  eggs,  at  both  poles  of  which  there  is  a 
knob-like  elevation. 

The  trichocephales  cannot  readily  be  expelled,  but  the  combined  adminis- 
tration of  anthelmintics  and  purgatives  will  give  the  best  results.  Besides 
santonin,  we  have  employed  successfully  the  ethereal  extract  of  male  fern. 
From  the  basis  of  his  experience,  Lutz  advises  thymol. 

Among  the  nematodes  which  are  of  great  pathogenic  importance  belong 
the  trichina  spiralis,  Owen,  1835,  and  the  anchylostoma  duodenale,  Dubini. 
1843.     I  shall  first  describe 

Trichina  spiralis, 

the  appearance  of  which  in  the  musculature  of  man  was  observed  by  Peacock 
in  1S28,  and  by  J.  Hilton  in  1833.  These  and  other  findings,  which  were 
looked  upon  only  as  interesting  secondary  findings  at  autopsies,  attained  their 
true  importance  in  I860  through  v.  Zenker.  In  a  case  observed  by  this  author, 
of  a  girl  who  was  dying  from  symptoms  resembling  enteric  fever,  numerous 
recently  entered  trichina'  were  found  in  the  muscles,  as  well  as  many  in  the 
intestine,  while  no  other  possible  cause  for  her  disease  was  evident.  The  same 
author  ascertained  that  in  the  district  in  which  the  patient  had  lived  a  num- 
ber of  milder  affections  had  occurred.  Sausages  ami  hams  which  wen1  still 
there  permitted  the  detection  of  massive  encapsulated  trichina.  From  this 
time,  the  attention  of  physician-  was  directed  to  trichiniasis.  It  was  soon  pos- 
sible, even  during  the  life  of  the  patient,  to  demonstrate  the  cause  of  the 
disease  in  the  musculature.  Abundant  material  was  furnished  by  the  "tri- 
china epidemics"  which  appeared,  particularly  in  Middle  Germany;  ami  the 
study  of  these  rapidly  added  to  our  knowledge  of  the  previously  absolutely 
unknown  disease,  both  clinically  and  pathologically,  and  enabled  us  to  reach 
definite  conclusions. 

Bui  not  only  in  Germany  was  trichinosis  observed;  it-  existence  was  Boon 
demonstrated  in  Switzerland,  England,  Denmark,  Sweden.  Russia,  France. 
Italy.  India.  Syria,  America  and  Australia.  Wherever  the  cause  could  be  ascer- 
tained, a  connection  with  the  ingestion  of  pnrlr  containing  trichina  was  proven. 
With  the  determination  of  this  fait  the  question  arose  a-  to  the  source  of 
trichina  for  the  -wine.  The  theory  that  piga  were  infected  by  the  ingestion 
of  rain-worms,  frogs  and  moles  containing  trichina'  was  soon  shown  to  be 
erroneous.     Leuckarfe  view,  promulgated  in   1862,  that  rats  were  the  actual 

BOtirce  of  infection    for  the  pig  w&B  "f   far-reaching  importance.      We  are  also 


554  THE  ANIMAL  PARASITES  OF  MAN 

indebted  to  v.  Zenker  whose  labors  have  proven  that  rats  become  infected  by 
the  ingestion  of  other  animals  containing  trichina.  Contagion  occurs  in  pigs, 
as  a  rule,  by  "eating  trichina-containing  meat  of  other  pigs."  As  is  well 
known,  some  parts  of  the  meat  are  often  utilized  for  feeding  swine,  particu- 
lar^ during  slaughter  time  in  the  country,  and  when  animals  are  skinned  offal 
containing  trichinae  is  often  given  to  pigs.  In  such  localities  it  is  obvious  that 
sufficient  waste  material  remains  to  infect  at  the  same  time  the  entire  colony 
of  rats  that  are  present.  The  latter  continue  to  be  for  years  a  further  source 
of  infection  for  the  pigs,  who  are  usually  expert  rat  catchers,  and  who  often 
eat  the  enemy  which  they  have  killed.  Wherever  pigs  infected  with  trichina 
are  slaughtered  without  the  complete  destruction  of  their  cadavers,  there  is 
danger  of  distribution  of  trichina.  Mature  trichinae  are  found  in  the  small 
intestine  of  the  rat,  the  wild  boar,  the  fox,  the  polecat,  the  marten,  the  raccoon 
and  the  cat,  as  well  as  in  man  and  in  swine.  Man  infects  himself  almost 
exclusively  by  the  ingestion  of  raw  or  insufficiently  cooked  pork,  which  con- 
tains the  so-called  muscle  trichina  in  a  condition  capable  of  development. 
Thorough  boiling  or  frying  will  kill  the  trichina,  provided  the  temperature 
in  the  inner  portions  of  the  meat  is  50°  to  55°  E.  Neither  decomposition  nor 
cold  diminishes  the  property  of  life  in  the  trichina.  Muscle  trichinae  retain 
their  power  of  development  for  many  years  (up  to  31).  Thorough  salting  de- 
stroys the  life  of  the  trichina,  but  it  is  certainly  not  destroyed  by  cold  smoking 
nor  in  the  so-called  rapid  smoking  process. 

The  encapsulated  trichinae  found  in  the  musculature  appear  as  small  gray 
nodules,  rarely  over  1  mm.  in  length,  and  consist  of  a  capsule  which,  as  in  the 
case  of  man,  after  the  lapse  of  years  becomes  calcified.  The  capsule  encloses 
the  trichina.  This  is  a  spiral  worm  of  0.6-1  mm.  in  length  and  0.01-0.03  mm. 
in  breadth ;  the  head  is  pointed,  the  tail  is  rounded ;  upon  the  head  is  the  mouth 
opening,  upon  the  tail  the  anus.  If  parts  of  muscles  permeated  with  living 
trichina?  reach  the  stomach  of  man,  of  the  pig  or  of  any  other  suitable  animal, 
the  gastric  juice  dissolves  the  capsule;  in  from  two  to  three  days  the  para- 
sites which  have  entered  the  intestine  attain  their  sexual  maturity.  Soon 
after  copulation  the  males  die,  while  the  females,  according  to  the  observations 
of  Askanazy,  actively  bore  into  the  intestinal  mucous  membrane,  and  seven 
to  nine  days  after  infection  has  taken  place  produce  living  young.  This  act  of 
bringing  forth  takes  place  usually  in  the  tissue  of  the  intestinal  mucous  mem- 
brane, that  is,  close  to  the  central  chyle  vessels  of  the  villi.  Probably  the 
majority  of  the  embryos  enter  the  circulation  directly  through  the  chyle  and 
lymph-vessels;  carried  by  the  blood-stream  they  wander  into  the  transverse 
striped  muscles.  Up  to  this  time  the  usual  mode  of  distribution  has  been 
assumed  to  be  migration,  i.  e.,  by  boring  through  the  intestinal  walls,  the  para- 
sites enter  the  peritoneal  cavity,  and  thence  the  connective  tissue  parts  of  the 
musculature ;  or  the  path  has  been  traced  through  the  submucosa,  through  the 
mesentery,  and  the  retroperitoneal  connective  tissue.  According  to  Askanazy, 
distribution  of  the  parasites  by  active  wandering  is  only  secondary.  About 
the  ninth  or  the  tenth  day  after  infection,  the  first  influx  of  parasites  reaches 
the  musculature.  The  female  is  so  immensely  reproductive  that,  for  about 
seven  weeks,  new  groups  of  parasites  constantly  find  their  way  there. 


NEMATODA,  THREAD-WORMS  555 

The  young  embryos  have  a  length  of  0.1  mm.,  a  breadth  of  0.006  mm.  The 
anterior  end  of  the  body  is  thicker  than  the  posterior.  After  entering  the  mus- 
cle, they  penetrate  still  more  deeply  into  its  interstitial  tissue,  in  a  longi- 
tudinal direction,  toward  the  insertions  of  the  tendons.  Their  path  through 
the  fibers  causes  a  number  of  changes  in  them.  The  trichina  has  a  destructive 
action  upon  the  finer  constituents  of  the  fibers.  These  lose  their  transverse 
striae  and  are  changed  into  a  fine  granular  mass.  Without  doubt  the  embryo 
is  nourished  by  the  decomposed  muscular  substance.  I  do  not  wish  to  be 
wearisome  with  the  finer  histologic  details,  and  shall  emphasize  only  the  fol- 
lowing points  in  the  development  of  the  muscle  trichina:  The  development 
occurs  in  about  fourteen  days.  The  muscle  trichina  gradually  grows  to  a 
length  of  0.1 .2-0. 10  mm.,  simultaneously  rolling  itself  into  a  spiral.  The 
sarcolemma  distributes  itself  about  the  embryo,  and  thickens.  In  the  inter- 
stitial tissue,  as  well  as  in  the  muscular  substance,  such  an  increase  of  the  mus- 
cle nuclei  occurs  that  the  trichina  appears  completely  embedded  in  them,  and 
surrounding  it  is  an  areola  of  granular  material  which  stains  more  intensely 
than  the  remaining  contents  of  the  nodule.  After  about  four  weeks  the  con- 
tents of  the  nodule  permeated  by  nuclei  enter  upon  a  process  of  reconstruction, 
which,  beginning  at  both  ends,  rapidly  reduces  these  ends  to  thin  threads. 
Around  the  spiral  swelling,  as  well  as  around  the  threads,  is  a  gelatinous 
sheath  which  Leuckart  recognized  as  thickened  sarcolemma.  Outside  of  this 
is  a  zone  of  inflammatory  connective  tissue  richly  supplied  with  connective 
tissue  corpuscles  and  leukocytes.  Later  the  disorganized  muscular  mass  in 
the  region  of  the  thread-like  processes  disappears.  The  connection  with  the 
material  surrounding  the  trichina  is  interrupted.  The  formation  of  a  clearly 
defined  trichina  capsule  now -begins;  starting  from  the  surrounding  con- 
nective tissue  cells,  probably  in  the  course  of  the  old  gelatinous  sheath,  the 
new  and  firmer  cyst  is  separated  from  the  encroaching  connective  tissue  cells. 
Fat  cells  develop  at  t lie  poles  of  the  capsules.  At  about  the  sixth  month  the 
capsule  begins  to  calcify  owing  to  a  deposit  of  calcium  carbonate.  This  cal- 
cification may  also  affect  the  enclosed  trichina.  According  to  Langerhans,  the 
trichina'  as  well  as  their  capsules  are  capable  of  retrogression  and  may 
finally,  although  only  after  many  years,  he  completely  eliminated  from 
the  body. 

In  man.  the  source  of  infection  i<  almosl  exclusively  the  pig,  very  rarely 
the  wild  boar  and  the  bear.  The  danger  of  transmission  of  trichina?  capable 
of  development  from  the  ingestion  of  infected  pork  depend-  upon  the  prepara- 
tion of  the  meat.     People  who  partake  of  infected  pork  raw  or  insufficiently 

cooked  show  the  nio-t  severe  symptoms.     Haw  at  in  the  form  of  so-called 

hadi.  boiled  fresh  pork  from  a  newly  killed  pig,  roast  sausage  or  German 
Bausage  (Knackwurst)  in  the  preparation  of  which  the  heating  is  insufficient 
to  insure  the  destruction  of  the  trichina  appear  to  be  especially  dangerous. 
The  ingestion  of  meal  of  this  kind,  which  i-  particularly  common  in  Middle 
and  North  Germany,  causes  the  frequent  appearance  <>f  the  disease  in  endemics 
and  epidemics.  In  the  Bixth  decade  of  the  last  century  severe  epidemics  of  this 
kind  were  observed  in  Plauen,  Hettstädt,  Fiedersieben.  In  South  Germany, 
and  in  other  countries,  France,  England,  Belgium,  America,  etc.,  this  custom 


556  THE  ANIMAL  PARASITES  OF  MAN 

does  not  prevail;  pork  is  either  well  cooked  or  boiled  or  smoked,  and  trichina 
epidemics  are  rare.  The  question  is  much  discussed,  whether  infection  may 
be  brought  about  by  the  importation  into  Germany  of  American  ham  and 
bacon.  According  to  Billings  trichinosis  is  met  with  in  American  pork  in 
4-5.7  per  cent.,  but  the  above  question  has  been  answered  in  the  negative  by  a 
majority  of  authors.  Some  observers,  however,  hold  a  directly  contrary  opin- 
ion. Caution  is  therefore  enjoined.  Nevertheless,  sporadic  cases  may  and 
will  occur  everywhere  in  the  future. 

No  age,  no  sex  is  exempt;  all  who  partake  of  infected  meat,  either  raw 
or  in  a  half-cooked  state,  are  attacked.  The  severity  of  the  disease  depends 
upon  the  amount  of  meat  and  the  number  of  trichinae  consumed.  Man 
appears  capable  of  harboring  a  certain  number  of  muscle  trichina1  without 
symptoms.  This  is,  at  least,  indicated  by  the  accidental  finding  of  muscle 
trichinae  at  the  autopsy  of  individuals  who  during  life  had  shown  no 
symptoms. 

The  symptoms  produced  by  trichinosis  correspond  to  the  phases  of  develop- 
ment of  the  trichinae.  Frequently,  a  few  hours  after  the  ingestion  of  meat 
containing  trichinae,  severe  gastric  and  intestinal  symptoms  appear:  Nausea, 
vomiting,  cardialgia,  vertigo,  headache,  heaviness  in  the  limbs,  constipation 
or  diarrhea.  If  the  infection  be  severe  the  symptoms  often  increase  and  simu- 
late a  severe  intestinal  catarrh,  which  in  isolated  cases  may  run  its  course 
with  choleraic  symptoms.  With  increasing  lassitude  a  more  or  less  decided 
fever  develops.  The  patients  become  bedridden,  v.  Linstow  quite  properly 
regards  the  severe  initial  intestinal  symptoms  as  toxic,  due  to  the  toxic 
products  which  have  been  set  free  by  the  dissolution  of  the  capsules.  The 
presence  of  intestinal  trichinae  in  the  dejecta  has  up  to  the  present  been  rarely 
demonstrated. 

In  many  cases,  initial  intestinal  symptoms  are  wholly  absent,  and  it  is 
therefore  impossible  to  determine  the  period  at  which  infection  occurred. 
There  are  indistinct  symptoms;  rheumatic  pains  in  the  limbs  and  fever;  indi- 
vidual muscles  begin  to  swell  and  become  edematous.  Briefly,  the  symptoms 
are  those  of  myositis.  Simon,  Kratz  and  Rupprecht  mention  as  characteristic, 
even  from  the  first  days  of  the  disease,  the  so-called  "  sympathetic  muscle  lame- 
ness." This  consists  in  a  drawing  sensation  in  the  limbs,  tension  and  tender- 
ness in  the  muscles,  such  as  is  observed  otherwise  only  after  unusual  muscular 
exertion.  The  flexors,  the  muscles  of  the  nape  of  the  neck,  and  those  of  the 
lumbar  region  are  particularly  involved.  Sometimes  in  the  first,  more  fre- 
quently in  tho  second,  week,  Kratz  observed  neuralgic  pains  in  the  abdomen 
which,  recurring  at  irregular  periods,  sometimes  as  often  as  six  times  in  the 
twenty-four  hours,  resembled  a  neuralgia  cceliaca. 

The  gastric  and  intestinal  disturbances  are  frequently  accompanied  by  fever. 
Only  in  mild  cases  is  this  absent  during  the  second  half  of  the  second  week, 
and  it  is  decidedly  increased  when  the  muscular  symptoms  become  manifest. 
Chilliness  frequently  accompanies  the  fever,  though  marked  chills  are  rare. 
The  maximum  rise  of  temperature  (104°  to  105.8°  F.)  is  usually  observed  from 
the  ninth  to  the  eleventh  day  after  the  beginning  of  the  malady.  At  first  con- 
tinuous, the  temperature  finally  shows  a  remittent  type.     The  return  to  nor- 


XEMATODA,  THREAD-WORMS  557 

mal  is  extraordinarily  slow.  This  is  markedly  different  from  the  temperature 
course  of  enteric  fever.  In  mild  cases,  even  during  the  third  week,  the  temper- 
ature falls  to  normal,  while  severe  cases  continue  to  show  a  febrile  range  from 
four  to  seven  weeks.  The  pulse  frequency  corresponds  to  the  height  of  the 
fever. 

In  the  course  of  the  second  week,  edema  of  the  face,  particularly  of  the 
eyelids,  is  characteristic.  After  several  days  this  may  disappear,  but  it  often 
returns  in  the  later  stages.  The  affection  of  the  muscles  is  accompanied  by 
marked  edema;  the  genital  region  often  remains  free. 

Usually  from  the  ninth  or  tenth  day — sometimes  earlier  or  later — with  the 
entrance  of  the  embryo  into  the  muscles,  symptoms  occur  there.  The  affected 
muscles  are  tensely  swollen,  as  hard  as  wood,  and  very  sensitive  to  touch  or 
pressure.  In  mild  cases  only  the  sensation  of  painful  tension  is  felt,  and  the 
patients  are  still  able  to  walk  about.  In  severe  cases  the  slightesl  movement 
is  accompanied  by  the  most  intense  pain:  locomotion  and  standing  are  im- 
possible. As  a  rule,  the  muscles  of  the  extremities  and  particularly  the  flexors 
are  the  most  painful.  In  order  to  relax  their  muscles  as  much  as  possible  the 
severe  cases  assume  a  characteristic  position:  Permanent  dorsal  decubitus  with 
an  acute  angle  contracture  in  the  shoulder,  elbow  and  wri>t  joint;  stiffness 
and  muscular  rigidity  are  observed  in  the  masseters,  in  the  muscles  of  the 
neck  and  of  the  upper  extremities.  Implication  of  the  muscles  of  deglutition 
and  of  the  tongue  often  causes  greal  difficulty  in  swallowing.  Hoarseness  and 
aphonia  result  from  the  involvement   of  the  muscles  of  the  larynx;  and  in 

re  cases  pain  in  the  muscles  of  the  eye  is  rarely  absent.  The  mobility  of 
the  eye-balls  is  affected,  and  this  gives  to  the  face  a  conspicuously  rigid  appear- 
ance, in  severe  cases,  the  masse-  of  trichinae  cause  difficulty  in  respiration; 
extreme  dyspneic  conditions  may  develop  with  very  severe  asthmatic  attacks, 
and  may  be  a  direct  cause  of  death. 

Even  at  the  beginning  of  the  second  week  Kratz  noted  inactivity  of  the 
diaphragm  upon  inspiration.  The  condition  noted  by  Askanazy  is  very  inter- 
esting. Tbi>  author  found  under  the  pleura  pulmonalis  and  in  the  lung  sev- 
eral disseminated  red  Hakes  or  point-  which  closely  resembled  the  punctiform 
ecchymo8es  upon  the  human  pleura.  These  were  demonstrated  to  be  young 
trichina'  which  had  formed  emboli. 

Changes  in  the  skin  are  nol  rare.  Besides  edema,  pruritus,  measle-like 
exanthema,  and  in  the  later  stages  acne,  furunculosis,  herpes,  etc.,  appear. 
The  sweats  which  occur  in  the  mild  as  well  as  the  Bevere  cases  are  particularly 
annoying.  Desquamation  of  the  skin  takes  place  in  convalescence.  Formica- 
tion and  cutaneous  anesthesia  have  been  observed  in  Isolated  cases. 

Stubborn  bronchial  catarrh  develops  early.  In  the  later  stages  hypostatic 
and  catarrhal  pulmonary  inflammations  occur.  In  debilitated  patients  these 
not  infrequently  cause  death. 

In  general  there  are  no  characteristic  changes  in  the  cardiac  activity.  In 
and  in  the  later  course  of  the  affection  thromboses  develop,  par- 
ticularly in  the  lower  extremities.  'The  appearance  of  decided  leukocytosis  with 
a  conspicuous  increase  of  the  eosinophiles,  which  show  an  increase  of  from 
30  per  cent,  to  60  per  cent.,  is  interesting.     This  demonstration  has  repeatedly 


558  THE  ANIMAL  PARASITES  OF  MAN 

aroused  a  suspicion  of  trichinosis  which  has  been  later  confirmed.  Perhaps 
the  eosinophilic  cells  originate  from  the  polymorphonuclear  neutrophilic  cells 
of  the  diseased  musculature. 

Lately,  in  isolated  cases,  the  temporary  absence  of  the  patella  tendon  reflex 
as  well  as  anomalies  of  the  electric  contractility  of  the  muscles  has  been  deter- 
mined. 

The  urine  shows  the  usual  characteristics  of  fever  urine.  Nonne  and 
Höpfner  have  recently  called  attention  to  the  not  infrequent  occurrence  of 
parenchymatous  nephritis.  Menstrual  irregularities  are  common  in  some 
epidemics.     In  pregnant  women  abortion  is  not  rare. 

Insomnia  is  one  of  the  chief  complaints  of  the  patient.  The  mind,  as  a 
rule,  is  perfectly  clear;  only  in  severe  cases  associated  with  high  fever  does 
delirium  occur. 

It  is  obvious  that  the  nutrition  must  suffer,  particularly  in  grave  cases. 

In  mild  cases  the  course  of  the  disease  is  from  one  to  two  weeks ;  in  all 
other  cases  one  to  two  months  intervene  before  recovery  takes  place.  Death 
is  not  rare.  The  mortality  varies  in  different  epidemics.  In  Hedersleben  the 
mortality  amounted  to  29.8  per  cent.,  in  Calbe  21  per  cent.,  in  Burg  20  per 
cent.,  in  Klein-Quenstedt  1-t  per  cent.  In  children  a  favorable  course  of  the 
affection  is  frequent;  recovery  often  takes  place  at  the  end  of  the  third  week. 
Complications  are  rare.  The  slight  predisposition  of  children  to  trichinosis 
may  be  accounted  for,  first,  by  the  lesser  activity  of  their  gastric  juice,  and 
secondly,  by  their  more  frequent  fecal  movements  in  consequence  of  which 
large  portions  of  meat  containing  trichina?  may  be  discharged. 

At  the  autopsy  the  intestines  reveal  but  slight  changes,  and  these  consist 
principally  in  a  catarrhal  condition  of  the  small  intestine.  Swelling  of  the 
solitary  glands,  of  Peyer's  patches,  and  of  the  mesenteric  glands  is  observed. 
In  the  intestinal  mucus,  up  to  the  seventh  week,  intestinal  trichinae  are  found. 
Spleen  is  normal  or  enlarged.  Fatty  liver  is  frequent.  Heart  muscles  and 
kidneys  often  show  granular  opacity.  Fatty  liver  and  nephritis,  according  to 
v.  Linstow  and  Askanazy,  are  due  to  the  toxic  products  of  metabolism  of  the 
trichina;.  The  lungs  usually  reveal  the  signs  of  a  marked  bronchitis.  The 
bronchial  mucous  membrane  is  intensely  reddened,  and  has  a  tenacious  mucus 
coating.  In  the  lower  posterior  portions  lobular  hepatization  is  revealed; 
rarely  hemorrhagic  infarcts  or  metastatic  abscesses.  The  color  of  the  muscles 
often  resembles  "  smoked  goose  breast " ;  the  smaller  muscles  are  much  paler 
and  "  wax-colored."  From  the  end  of  the  fifth  week  macroscopic  changes  in 
the  form  of  pale  gray  striae  of  from  \  to  1  cm.  in  length  may  be  recognized. 
Upon  microscopic  examination  these  are  seen  to  be  dark,  granular,  detritus- 
like masses.  Granular  and  fatty  degeneration,  sometimes  also  waxy  degen- 
eration, are  found  in  the  surrounding  muscle  fibers.  Not  rarely  giant  cell- 
like structures  are  noted.  Nonne  and  Höpfner  describe  the  appearance  of 
vacuoles  in  the  muscle  fibers.  In  the  later  stages  this  musculature  dis- 
appears to  a  great  extent  and  is  pale.  The  number  of  muscle  trichina? 
may  be  enormous.  The  most  intense  permeation,  according  to  Cohnheim, 
is  found  in  the  diaphragm,  in  the  intercostals,  in  the  muscles  of  the  neck, 
of  the  larynx  and  of  the  eyes,  of  the  biceps  and  triceps.     In  milder  cases 


NEMATODA,  THREAD-WORMS  559 

the  presence  of  a  single  trichina  may  be  demonstrated  only  after  a  search 
of  hours. 

The  prognosis  cannot  he  determined  in  the  early  stages  of  tho  disease. 
Severe,  fulminant  phenomena,  especially  on  the  part  of  the  digestive  appa- 
ratus, are  not  necessarily  followed  by  a  severe  course,  as  the  diarrheal  dis- 
charges remove  a  portion  of  the  infectious  material.  Cases  which  appear  mild 
at  the  onset  may  subsequently  become  very  severe.  After  a  course  of  three  to 
four  weeks,  those  cases  in  which  the  patient  retains  a  good  appetite  and  the 
ability  to  sleep,  as  well  as  the  integrity  of  the  respiratory  organs  and  of  the 
heart,  permit  the  hope  of  a  favorable  outcome.  In  children  the  prognosis  is 
more  favorable  than  in  adults  from  the  onset. 

During  the  prevalence  of  epidemics,  the  diagnosis  is  more  readily  made 
than  in  sporadic  cases. 

Mild  cases  may  simulate  gastric  catarrh  and  muscular  rheumatism:  severe 
cases  resemble  acute  gastro-intestina]  catarrh,  and  in  their  further  course  may 
be  looked  upon  as  acute  articular  rheumatism.  The  edema,  the  painfulness 
of  the  affected  muscle  groups,  the  impairment  of  respiration,  are  important 
in  diagnosis.  The  differentiation  from  acute  progressive  polymyositis  is  not 
always  easy.  In  doubtful  cases  it  is  well  to  search  the  dejecta,  particularly 
the  intestinal  mucus,  for  intestinal  trichina*.  In  severer  infections  the  tri- 
china? may  certainly  be  determined  by  the  excision  of  small  portions  of  mus- 
cle, which  are  best  taken  from  the  lower  end  of  tbe  biceps.  Direct  excision  is 
decidedly  preferable  to  the  formerly  practised  harpooning. 

The  aim  of  the  prophylaxis  should  be  the  prevention  of  trichinosis  in  the 
pig.  Stall  feeding  of  swine  gives  in  this  respect  a  certain  protection,  espe- 
cially if  care  is  taken  never  to  feed  them  with  uncooked  offal,  lit  regions 
where  trichinosis  frequently  occurs  a  thorough  inspection  and  radical  destruc- 
tion of  meal  containing  trichina'  should  be  obligatory.  Tbe  keeping  and  fat- 
tening of  -wine  in  Blaughter-houses  should  be  prohibited. 

Man  i-  besl  protected  from  tbe  disease  by  eating  only  thoroughly  boiled 
or  well-fried  pork.  Tbe  mosl  intense  smoking  or  pickling  will  kill  the  para- 
rite,  but  these  precautionary  measures  are  not  everywhere  taken.  There  may 
be  exposure  to  infection,  for  example,  upon  a  journey.  Tbe  most  important 
preventive  measure,  therefore,  is  the  erection  of  slaughter-houses  and  the 
introduction  of  compulsory  meat  inspection.  Tbe  microscopic  demonstration 
of  muscle  trichinae  is  not  difficult,  and  this  may  be  carried  out  by  thoroughly 
competent  meat  inspectors.  Absolute  protection,  naturally,  cannot  be  con- 
ferred by  meat  inspection  if  only  a  (^w  muscle  trichinae  are  present.  It  is 
well,  therefore,  to  carefully  abstain  from  partaking  of  any  but  thoroughly 
cooked  or  highly  pickled  or  smoked  pork. 

We  are  vrery  rarely  in  a  position  to  begin  treatment  soon  after  infection  has 
taken  place,  but.  wben  tins  is  possible,  emetic-  and  purgatives  are  advisable. 
Theoretically,  an  attempt  should  be  made  to  expel  the  infection-  masses  by  the 
administration  of  castor  oil,  calomel,  etc.  Experimentally,  it  is  true,  do  re- 
markable results  ba\c  followed  tbi-  <>r  any  other  method  of  treatment.  Neither 
potassium,  oor  -odium  picronitrate,  nor  oil  of  turpentine,  camala,  extract  of 
male  fern,  glycerin,  etc.,  has  prevented  infection. 


560  THE  ANIMAL  PARASITES  OF  MAN 

Mosler,  upon  the  basis  of  experimental  investigation,  has  advised  benzine: 

^  Benzoli : 6.0, 

Mucil.  gummi  arab 25.0, 

Succi  liquir 8.0, 

Aqua  menth.  pip 120.0. 

M.D.S.     Well  shaken,  a  tablespoonful  every  hour  or  two. 

Besides  this  Mosler  advises  daily  for  several  days  an  enema  to  which  is  added 
three  to  eight  grams  of  benzine.    In  the  main  the  treatment  is  symptomatic. 

For  the  sake  of  completeness  I  shall  mention  among  other  nematodes  the 
eustrongylus  gigas,  Eudolphi,  1802,  a  parasite  which  is  found  in  the  renal 
pelvis  of  the  dog,  the  wolf,  the  fox,  the  horse,  the  marten,  the  otter,  etc.,  and 
has  been  observed  in  man  in  about  nine  different  cases.  The  parasite  has  fre- 
quently been  confounded  with  other  nematodes,  with  coagula  of  blood,  or  with 
mucus.  According  to  experiments  conducted  in  the  dog,  the  eustrongylus 
causes  severe  difficulty  in  urination.  The  ova  of  the  parasite  may  be  recognized 
in  the  urine.  The  strongylus  paradoxus,  Mehlis,  1831,  has  been  even  less  fre- 
quently observed  in  man. 

Gnathostoma  siamense,  Levinsen,  1889,  has  up  to  the  present  been  seen 
by  Levinsen  only  as  one  female  specimen  in  a  Siamese  and  in  two  other  persons. 


ANKYLOSTOMI ASIS— UNCINARI A  SI  S 

One  of  the  most  important  entozoa  of  man  is  the 

Ankylostoma  duodenale,  Dvbini,  1843. 

The  parasite  was  first  discovered  by  Dubini  in  1838  in  Milan  in  a  human 
cadaver.  Soon  its  occurrence  was  also  noted  by  Pruner,  Bilharz  and  Griesin- 
ger  in  Egypt.  The  parasite  was  recognized  by  Bilharz  and  Griesinger  on 
account  of  its  hematophagous  properties  as  the  actual  cause  of  "  Egyptian 
chlorosis,"  which  is  so  extraordinarily  prevalent  in  Egypt. 

Wucherer,  in  1866,  recognized  the  parasite  as  the  cause  of  "  tropical  chloro- 
sis." Its  presence  was  soon  afterward  determined  in  the  anemia  of  trick- 
makers,  which  had  been  known  for  a  long  time  in  Italy.  Parona,  Perroncito, 
Bozzolo  found  the  parasite  associated  with  the  anemia  which  attacked  the 
workmen  engaged  in  constructing  the  Saint  Gothard  tunnel,  and  looked  upon 
it  as  the  causal  factor.  Soon  the  proof  of  its  connection  with  anemia  mon- 
tana  which  occurred  in  the  Belgian,  Sardinian  and  French  mines  in  1882  was 
established.  The  occurrence  of  the  parasite  was  recognized  by  Mencke  in  the 
brickmakers  in  the  neighborhood  of  Bonn,  and  a  few  weeks  later  by  Leichten- 
stern  among  the  workmen  in  the  brick  fields  at  Cologne. 

Since  that  time  its  occurrence  has  also  been  proven  in  the  miners  of  the 
Rhine  provinces,  Westphalia  and  Silesia,  sometimes  in  wide  distribution. 

The  male  parasite  is  usually  of  a  white,  the  females  of  a  whitish  yellow, 
brownish-red,  or  reddish  color.  The  length  of  the  male  averages  from  7-11.2 
mm.,  the  thickness  0.46  mm.;  the  females  are  16.5  mm.  long  and  0.63  mm.  in 


ANKYLOSTOMIASIS— UNCINARIASIS 


561 


thickness.  The  parasite  tapers  toward  the  anterior  extremity.  The  intestinal 
tract  begins  with  a  wide  slanting  mouth,  turned  toward  the  back  and  having 
six  papillae;  it  has  a  bell-like  mouth  capsule,  upon  the  border  of  which  are  six 
tooth-like  chitin  ridges.  The  posterior  end  of  the  body  of  the  female  termi- 
nates in  a  short  ten-pin-like  point;  that  of  the  male  is  somewhat  bent,  termi- 
nating in  a  broad  umbrella-like  ribbed  bursa  copulatrix.  upon  which  frequently 
two  long  spicula  of  about  2  mm.  in  length  protrude.  The  bursa  copulatrix 
serves,  on  account  of  its  contractile  parenchyma  ribs,  as  an  apparatus,  by 
means  of  which  the  males  attach  themselves  to  the  body  of  the  female  during 
copulation.  The  female  sexual  opening  is  close  behind  the  middle  of  the  body, 
and  is  continued  as  a  short  vagina.  The  parts  next  to  the  vagina  contain  the 
impregnated  ova.  These  have  an  oval  shape  and  a  smooth  surface.  Their 
length  is  0.063  and  their  thickness  from  0.036-0.04  mm.  They  are  present 
in  enormous  numbers  in  the  human  dejecta  and.  according  to  the  time  in 
which  they  have  remained  in  the  intestinal  canal,  2  or 
4-8  segmentation  globules  may  be  recognized.  Further 
development  occurs  only  outside  of  the  human  organism. 
For  this  development  the  ova  require  a  temperature  of 
from  25°  to  30°  C,  moderate  moisture,  and  a  surface 
distribution.  Under  these  circum- 
stances, after  three  to  four  days  at 
fö  the  Latesl  the  embryo  may  be  recog- 

W  1^1  nized.      After  twenty-four  to  forty- 

eighl  hours  more,  it  finds  its  way 
through  the  pole  of  the  ova,  and 
shows  active  movements. 


Fig.  54.  —  Anktlosto- 

M  \       I  )l   (HUN  Ml    :      ", 

male:  b,  female. 


Fig.    5.5. — Ova    ok   the   Ankylostoma 

Im  od]  \\i.i;    iv   Varioi  -   Eh  \<;ks  of 
I  u  \  I  I  OPMEN  i . 


Fig.   56. —  Larva   <>k 

Anki  LOSTOMA  Dl  "- 

D]  \  \i  I  . 


The  young  larva  ia  0.2  0.25  mm.  in  length  and  0.015-O.On  mm.  in  thick- 
ness. The  posterior  end  of  the  body  gradually  tapers  anteriorly  to  a  pouch; 
like  point.  The  -bort  and  narrow  opening  of  the  mouth,  the  spindle-shaped 
pharynx,  and  the  globular  stomach  may  be  distinctly  recognized;  in  the  latter 
a  Y-diaped  figure,  composed  of  the  three  pharyngeal  teeth,  is  found  in  active 
movement.  The  intestine  terminates  in  a  fine  tube,  the  anus.  The  embryo 
soon  begins  to  grow,  and  after  having  attained  a  length  of  0.1  0.8  mm.  it 
encapsulates  itself.  The  larva  finally  lies  in  a  transparenl  sheath  which  uni- 
formly Burrounds  it.     The  sheath  protect-  tl mbryo  from  external  damage, 

so  thai  for  months  in  tin-  encysted  -täte  it  may  retain  it-  power  of  further 
development.  Introduced  into  (be  human  intestine,  after  dissolution  of  its 
chitin  capsule  in  the  -mall  intestine,  the  parasite  develops  to  maturity.     I 


562  THE  ANIMAL  PARASITES  OF  MAN 

to  six  weeks  after  infection  has  taken  place  the  first  ova  appear  in  the  human 
dejecta. 

The  parasites,  as  well  as  the  symptoms  which  are  included  under  the  name 
ankylostomiasis,  have  heen  found  exclusively  in  those  persons  who  labor  in 
any  way  in  the  earth ;  miners,  tunnel  workmen,  brickmakers,  laborers  upon 
fortifications,  etc.  The  dejecta  voided  by  an  ankylostoma  host  are  exceed- 
ingly rich  in  ova,  as  shown  by  the  interesting  observations  of  Leichtenstern 
in  the  brick  fields  of  Cologne,  and  they  are  the  source  of  infection  for  other 
workmen.  The  fecal  masses  deposited  in  the  outskirts  of  the  brick  fields,  with 
the  gradual  advance  of  the  work  contaminate  the  layers  of  clay  and  become 
mixed  with  the  water.  Thus  there  is  abundant  opportunity  for  the  importa- 
tion of  encysted  larva?.  The  workmen  eat  their  meals  with  dirty  clay-cov- 
ered hands,  and  in  their  various  manipulations  of  the  clay  and  earthworks, 
in  cleaning  their  tools,  in  the  use  of  drinking-water  and  water  for  other  pur- 
poses, there  are  numerous  opportunities  for  the  encysted  ankylostoma  to  find 
their  way  into  the  human  organism.  Miners  and  tunnel  laborers,  and  espe- 
cially the  country  population  in  Egypt,  Brazil  and  other  countries,  infect 
themselves  in  a  similar  manner.  In  the  country,  particularly,  with  its  limi- 
tations and  the  absence  of  systematic  hygiene,  there  are  numerous  favorable 
conditions  for  the  propagation  of  the  parasites.  In  a  damp,  flat  country 
where  the  earth  is  only  slightly  permeable  and  there  is  an  absence  of  suitable 
latrines,  discharge  of  the  dejecta  filled  with  ova  in  the  immediate  vicinity  of 
laborers  and  living  places  must,  under  any  circumstances,  convey  the  germs  to 
the  inhabitants  and  laborers.  Loos  recently  called  attention  to  the  fact  that 
the  young  embryo  may  enter  the  human  organism  by  means  of  the  skin. 

The  number  of  parasites  is  frequently  very  great:  One  hundred,  500,  1,000 
and  more  have  been  found  in  the  small  intestine.  They  are  blood-suckers, 
kclt  e|ox^v;  and  when  we  consider  that  their  duration  of  life  is  relatively 
long — Leichtenstern  estimates  the  maximum  at  five  years — and  that  repeated 
infection  in  one  and  the  same  individual  in  infected  regions  is  probably  the 
rule,  we  can  clearly  understand  the  effects  of  this  parasite,  which  is  a  blood- 
sucker. 

Three  to  four  weeks  after  infection  the  first  symptoms  appear.  Besides 
dyspeptic  difficulties,  these  consist  especially  of  colic,  diarrhea,  increasing 
lassitude,  disinclination  to  work,  pallor  of  the  face.  Tinnitus  aurium,  ver- 
tigo and  cardiac  palpitation  are  added.  The  continuous  withdrawal  of  blood 
in  the  course  of  weeks  or  months  leads  gradually  to  the  most  extreme  symp- 
toms of  anemia.  Edema,  dyspnea,  and  attacks  of  syncope  develop  upon  the 
slightest  bodily  exertion.  The  dejecta,  often  even  five  to  six  weeks  after  infec- 
tion, have  a  hemorrhagic  appearance;  they  are  grayish  red,  brownish  red  or 
black.  Usually  the  first  hemorrhagic  diarrheic  discharges  occur  from  five  to 
six  weeks  after  invasion  of  the  larva?;  during  a  time,  therefore,  in  which  the 
parasites  frequently  change  their  situation  for  the  purpose  of  copulation.  In 
the  later  course  of  the  affection  symptoms  of  extreme  anemia  develop  in  the 
patients  who  have  become  bedridden. 

The  pulse  is  rapid  and  thready.  The  carotids  show  active  pulsation.  In 
the  heart,  which  is  frequently  enlarged  to  percussion,  there  are  systolic  mur- 


ANKYLOSTOMIASIS— UNCINARIASIS  563 

murs;  over  the  jugular  vein  distinct  nun's  murmurs  may  be  recognized.  Oc- 
casionally an  organic  cardiac  affection  develops.  As  a  rule,  there  is  a  diminu- 
tion in  the  number  of  red  blood-corpuscles,  the  amount  of  hemoglobin  is 
decidedly  reduced;  sometimes  there  is  leukocytosis.  The  Lungs  are  usually 
normal,  provided  accidental  complications  are  not  present.  The  microscopic 
examination  of  the  feces  shows,  besides  more  or  less  altered  blood  cells,  the 
presence  of  countless  ova  which,  as  a  rule,  are  uniformly  distributed  through 
the  entire  fecal  mass.  Almost  invariably  Charcot-Leyden  crystals  are  found. 
The  parasite  itself  is  generally  only  detected  in  the  feces  after  the  administra- 
tion of  anthelmintics. 

With  increasing  severity  of  the  disease  the  patients  show  the  distinct  symp- 
toms of  progressive  anemia.  Edema  develops  in  the  extremities  and  in  the 
face,  and  to  this  are  added  frequent  attacks  of  fever.  Changes  in  the  eye- 
ground,  edema  of  the  papilla,  and  effusions  of  blood  into  the  retina  have 
frequently  been  observed.  In  some  cases  bone  pains  are  noted  ;  Leichten- 
stern  in  such  a  case  observed  >imultaneously  a  decided  enlargement  of  the 
spleen. 

The  majority  of  the  severe  anemic  phenomena  may  probably  be  explained 
by  the  blood-absorbing  properties  of  the  parasite.  The  ankylostoma  are.  as  it 
were,  Luxurious  blood-absorbers,  since  they  nourish  themselves  only  from  the 
blood-plasma,  while  the  red  blood-corpuscles  leave  the  intestinal  canal  of  the 
parasite  in  an  unchanged  condition.  The  loss  of  blood  by  secondary  hemor- 
rhage from  the  wound.-,  particularly  during  the  time  in  which  the  parasites 
frequently  change  their  position  for  the  purpose  of  copulation,  is  perhaps 
even  greater  than  the  amount  of  blood  absorbed.  Lussano,  by  very  interesting 
investigations,  believes  he  has  proven  that  the  ankylostoma  give  off  like  other 
entozoa  toxic  product>  of  metabolism  which  have  a  deleterious  effect  upon 
the  blood.  Ervant,  Arstan,  Verdun,  Zinn  and  Jacoby  and  others  have  ex- 
pressed the  opinion  that,  besides  a  blood-sucking  activity,  there  is  probably  a 
toxic  effect  upon  the  blood  which  is  an  important  factor  in  the  origin  of  ane- 
mia. Bohland  has  determined  an  abnormally  great  decomposition  of  albumin 
in  ankylostoma  patient-. 

If  the  disease  is  not  recognized,  if  there  is  no  relief,  the  debilitated  patient 
suffers  for  week«  ami  months,  and  anally  succumbs  with  the  symptom-  of 
genera]  marasmus;  or  intercurrent  affections  terminate  lite.  Only  rarely 
does  a  change  of  climate  and  of  the  mode  of  life  bring  about  a  spontaneous 
recovery. 

The  cadavers  of  patients  who  die  of  ankylostomiasis  are  usually  but  Little 
emaciated,  provided  the  cases  have  been  uncomplicated,  but  they  are  invariably 
pair  and  w axy-yellow.  The  panniculu-  adiposus,  the  fa i  in  the  mesentery, 
in  the  heart,  and  in  the  mediastinum,  is  often  decidedly  increased.  The  mus- 
cles are  pale;  general  dropsical  phenomena,  including  hydrothorai  and 
hydropericardium,  are  common.  There  is  marked  anemia  of  all  organs. 
The  heart  muscle  i-  often  dilated,  hypertrophied,  pale  or  grayish-brown.  Tin» 
liver  and  spleen  are  more  or  Less  atrophic,  and  occasionally  show  amyloid  de- 
generation. Similar  changes  are  often  noted  in  the  kidneys.  The  small  intes- 
tine is  in  some  cases  decidedly  narrowed,  the  colon  sometimes  -how-  -ign-  of 


564  THE  ANIMAL  PARASITES  OF  MAN 

chronic  catarrh.  In  the  duodenum,  but  especially  in  the  jejunum  and  the 
upper  portion  of  the  ileum,  there  are  numerous  small  punctiform  ecchymoses. 
If  the  necropsy  is  carefully  conducted,  an  extraordinary  number  of  red-stained 
ankylostoma  are  occasionally  found.  These  ankylostoma  have  gained  en- 
trance into  the  mucosa,  and  cannot  be  removed  without  a  certain  amount  of 
force.  At  the  point  of  adherence  the  mucosa  reveals  ecchymosed  red  plaques 
of  a  punctated,  dappled  appearance  which  vary  in  size  from  a  five-cent  piece 
to  a  half-dollar.  It  is  more  difficult,  as  a  rule,  to  find  the  males  than  the 
females,  because  the  former  have  a  more  delicate  structure,  and  are  therefore 
less  noticeable  in  the  mucus.  The  mesenteric  glands  are  sometimes  enlarged. 
Masius  and  Francotte  found  that  the  bone-marrow  of  the  long  tubular  bones 
was  grayish  red ;  occasionally  it  is  rich  in  fat  and  is,  therefore,  more  yellow. 
Numerous  medullary  cells  and  nucleated  red  corpuscles  are  found  upon  micro- 
scopic examination. 

Secondarily  other  entozoa  have  been  found:  Among  them  anguillula  in- 
testinalis and  stercoralis  ascaris  lumbricoides,  oxyuris  vermicularis  and  tenia 
saginata. 

The  aim  of  prophylaxis  is,  first,  to  prevent  the  entrance  of  the  parasite 
into  regions  not  yet  affected,  and,  secondly,  to  limit  its  spread  in  the  infected 
areas.  To  attain  the  first  object,  in  the  future  no  workmen  should  be  em- 
ployed in  brickyards,  in  mines,  in  tunnels,  and  other  earthworks  until  their 
state  of  health  has  been  carefully  investigated,  and  their  feces  microscopically 
examined  for  the  presence  of  ankylostoma  ova.  Furthermore,  the  workmen 
should  be  taught  that  if  necessary  care  is  exercised  in  constructing  privies 
the  contamination  of  working  places  with  infected  dejecta  from  an  accumula- 
tion of  feces  can  be  entirely  prevented.  Those  who  know  the  habits  of  labor- 
ers and  their  carelessness  as  to  where  they  discharge  their  feces,  will  under- 
stand that  even  most  stringent  hygienic  rules  will  be  imperfectly  carried  out. 
The  best  prophylaxis,  therefore,  consists  in  employing  only  healthy  workmen, 
i.  e.,  those  not  infected  with  ankylostomiasis. 

If  ankylostomiasis  has  been  diagnosticated  by  examination  of  the  feces, 
the  patient  must  enter  the. hospital,  and  undergo  treatment  for  the  expulsion 
of  the  parasite.  Leichtenstern,  who  has  probably  had  the  largest  experience 
in  Germany  in  the  treatment  of  ankylostomiasis,  advises  the  administration, 
without  preliminary  treatment,  of  the  ethereal  extract  of  felix  mas  which  he 
gives  in  a  dose  of  ten  grams.  The  drug  is  given  after  breakfast.  From  one 
to  two  hours  later  a  suitable  dose  of  castor  oil  is  administered  to  the  patient. 
The  entozoa  voided  with  the  dejecta  will  have  been  killed.  If,  in  the  course 
of  a  few  days,  ankylostoma  ova  are  still  found  in  the  feces,  the  same  treatment 
must  be  repeated,  a  second  or  even  a  third  time,  until  the  ova  are  no  longer 
detected  in  the  feces.  Bozzola  advises  thymol  (2  to  10  grams  per  day)  ;  other 
authors  also  look  upon  this  drug  as  a  useful  anthelmintic.  It  is  evident  that, 
on  acccount  of  the  extreme  anemia,  a  symptomatic  treatment  for  this  condition 
must  in  many  cases  be  employed  during  convalescence. 

v.  Linstow  recently  described  a  representative  of  the  genus  physaloptera, 
physaloptera  caucasica  n.  spr.,  as  a  parasite  of  man.  This  was  found  by  v. 
Linstow  in  the  previously  mentioned  helminthic  collection. 


ARTHROPODA  565 

Blanehard  recently  called  the  attention  of  physicians  to  the  occurrence  of 
some  varieties  of  gordius — small,  elongated,  thin  worms  having  the  shape  of 
filarise — as  occasional  parasites  of  man.  He  spoke  particularly  of  the  gordius 
aquaticus,  gordius  argillaceus  and  gordius  medinensis,  which  live  in  fresh 
water,  notably  in  the  springs  of  mountainous  regions.  They  are  introduced 
into  the  human  intestinal  tract  by  drinking-water,  as  well  as  by  the  ingestion 
of  fruit,  and  are  finally  voided.  In  all  about  seven  transmissions  have  heen 
observed. 

Almost  as  rare  in  man  is  the  occurrence  of  the  acanthocephala,  a  nematode- 
like  parasite  withoul  intestines  whose  anterior  end  is  armed  with  a  proboscis. 
The  echinorhynchus  gigas,  Goeze,  L782;  is  found  in  great  uumbers  in  the 
small  intestine  of  swine.  According  to  Leuckart  its  presence  in  man  has  been 
proven  in  a  few  cases.  Lamb)  once  observed  the  echinorhyncus  hominis.  It 
has  heen  shown  by  artificial  infection  experiment-  that  echinorhyncus  monili- 
formis,  Bremser,   lSl'.),  may  occur  in  man. 

Hirudines  have  been  observed  as  occasional  parasites  of  man.  and  may  he 
transmitted  to  man.  Even  now  they  are  frequently  \\>^<\  for  medicinal  pur- 
poses. Among  them  have  heen  noticed:  Hirudo  medicinalis,  Linne,  L758, 
Hirudo  troctina,  Johnston,  L816,  Hirudo  ceylonica  Bl..  Limnatis  nilotica, 
Savigny,  1820.  These  are  found  ujion  the  skin  or  in  the  oral  cavity  of  man, 
and  soon  begin  their  blood-sucking  activity. 

ARTHROPODA 

Tin'  arthropoda,  particularly  the  arachnoids,  the  spiders  and  the  insects, 

are  found  in  great  numbers  as  parasites  of  man.     Owing  to  their  manner  of 
life  they  appear  chielly  a-  ectoparasites.      To  these  belong  the 

Leptus  autumnalis,  Shaw,  L790. 

The  so-called  gooseberry  or  harvest  acarus,  which  i<  0.3-0.5  mm.  long, 
and  nf  a  reddish  color,  lives  in  great  numbers  through  the  summer  in  immature 
forms  on  grass  and  shrubs,  and  occasionally  as  parasites  upon  man  and  other 
mammals.  The  ova  of  the  trombidium  holosericum,  which  are  conspicuous 
in  many  gardens  by  t heir  red  color,  are  deposited  in  dune  or  July.  Prom  these 
a  larva  develops  which  we  recognize  a-  the  leptus  autumnalis.  This  larva  bores 
into  the  skin  with  it>  head  and  produces  a  severe  cutaneous  inflammation  with 
itching  which  may  he  relieved  by  washing  with  soap,  by  inunction-  with  bal- 
sam of  Peru,  ot  ö  per  cent,  of  carbolic  solution  or  benzine. 

Similar  varieties  of  acarus  such  as  tetranyehus  molestissimus,  Weyen- 
bergh,    1886,   pediculoides  ventricosus,   Newport,    1850,   tarsonemus   intectus, 

Karpelles.  1885,  pygmephorus  ancinatus,  Flemming,  1884,  have  1 n  found  in 

workmen  who  had  handled  Indian.  Bulgarian  or  Russian  grain,  and  suffered 
from  an  itching  skin  eruption.  Other  varieties  of  acarus  cheyletus  eruditus 
(Schrank,  1781),  and  tydeus  molestus  (Monig)  which  are  found  In  rags, 
stables,  and  tobacco  stores,  also  attack  man  and  give  rise  i<>  distressing  itching. 

The  dermanyssus  avium  (Duges,  1834),  the  bird  acarus,  i-  better  known. 
It  occurs  in  chicken-,  pigeons  and  in  our  song  birds  wlun  kept  in  cages;  it 


566  The  animal  parasites  of  man 

occasionally  becomes  parasitic  in  man,  and  produces  very  intense  itching, 
erythema  and  eczema.  The  acarus  which  is  found  in  swallows,  dermanyssus 
hirudinis,  Hermann,  1804,  also  occasionally  becomes  parasitic  in  man. 

Of  the  ticks  the  ixodes  ricinus  Linne,  1758,  is  parasitic  in  man.  The  para- 
site lives  upon  low  bushes  and  generally  attacks  sheep,  cattle,  dogs,  cats,  and, 
not  rarely,  also  man.  The  female  bores  with  its  proboscis  deeply  into  the 
skin  to  suck  blood.  It  is  necessary  to  exercise  caution  in  removing  the  insect, 
as  the  proboscis  tears  readily,  and  if  left  in  the  wound  causes  inflammation. 
The  application  of  benzine,  petroleum,  or  oil  of  turpentine  readily  removes  the 
parasite. 

Not  quite  so  harmless  is  the  bite  of  the  argas  reflexus,  Fabricius,  1794. 
It  lives  in  woodwork  or  masonry,  and  in  some  regions  attacks  pigeons.  It 
occasionally  becomes  parasitic  in  man.  The  parasite  produces  local  inflamma- 
tion and  also  certain  general  symptoms,  among  which  are  nausea,  pyrosis,  diar- 
rhea, irregular  heart  action  and  dyspnea.  The  poison  is  said  to  be  contained 
in  the  powerfully  developed  salivary  glands.  The  bite  of  the  argas  persicus, 
Fischer  de  Waldheim,  1824,  and  of  the  argas  tholozani,  Laboulbene  et  Meg- 
nin,  1882,  which  live  in  Persia,  is  said  to  be  dangerous.  In  the  tropics  still 
other  members  of  the  family  of  argas  are  known  (such  as  the  argas  turicata 
Duges,  argas  chincha,  Gervais,  etc.),  which  occasionally  attack  man  and  pro- 
duce disagreeable  symptoms.  Of  the  family  of  the  tyroglyphides  only  the 
tyroglyphus  farina?,  de  Geer,  and  the  tyroglyphus  siro,  Linne,  the  tyroglyphus 
longior.  Gervais,  are  to  be  mentioned  as  occasionally  parasitic  in  man.  More 
important,  on  account  of  the  extent  of  its  distribution,  is  the  family  of  sar- 
coptes : 

Sarcoptes  scabiei,  Linne,  1748. 

The  knowledge  of  scabies  dates  back  to  antiquity.  Aristotle  was  appar- 
ently acquainted  with  the  organism.  But  although  the  insect  was  familiarly 
known  for  centuries,  its  natural  history  having  been  correctly  described  and 
depicted,  its  parasitic  character  was  not  recognized,  and  the  itch  was  looked 
upon  as  a  disease  produced  by  an  acrimonia  sanguinis.  This  opinion  became 
the  prevalent  one.  It  was  not  until  1834,  when  the  completely  forgotten  art 
of  catching  the  acarus  was  revived,  that  the  pathology  of  the  itch  was  recon- 
structed, and  the  acarus  generally  recognized  as  the  cause  of  the  affection.  It 
is  hardly  necessary  to  give  here  a  description  of  the  acarus.  A  microscopic 
preparation  of  the  acarus  may  readily  be  obtained ;  in  a  patient  with  the  itch 
we  look  for  a  large  pit  which  may  frequently  be  seen  with  the  naked  eye. 
This  pit  is  seen  upon  the  hands  as  a  blackish  line,  and  upon  the  trunk  as  a 
whitish  punctated  line.  At  the  end  of  this  groove,  where  a  whitish  discolored 
point  may  be  recognized,  the  epidermis  should  be  carefully  removed  with  a 
cataract  needle,  and  the  insect,  which  has  been  laid  bare,  can  be  extracted  and 
put  upon  a  slide. 

We  can  easily  recognize  upon  the  head  the  scissors-like  jaw  feelers  with 
which  the  impregnated  female  cuts  or  bores  its  way  into  the  epidermis.  Grad- 
ually it  penetrates  the  deeper  layers  of  the  rete  Malpighii.  The  bite  is  fol- 
lowed by  the  deposit  of  an  exudate  between  the  cutis  and  the  newest  epidermis 


ARTHROPODA  567 

layer  from  which  the  acarus  is  extracted :  decided  itching  immediately  arises, 
perhaps  in  consequence  of  the  discharge  of  an  irritating  fluid.  Boring  its  way 
transversely  from  without  inward  to  deposit  its  eggs,  the  acarus  makes  a  pas- 
sage parallel  with  the  first  to  the  surface  of  the  skin.  From  the  eggs,  about 
50  in  number,  deposited  in  this  passage  an  embryo  develops,  which  after  from 
four  to  seven  days  makes  its  own  opening  to  the  external  skin.  After  a  short 
time  it  again  bores  it-  way  into  the  skin  to  pass  through  a  desquamation  proc- 
ess, which  i<  repeated  several  times,  and  about  fourteen  days  later  it  appears 
as  a  mature  insect  upon  the  skin.  The  male  does  not  bore  its  own  opening, 
but  only  hollows  out  a  funnel-like  groove  in  which  it  lives. 

The  transmission  of  the  acarus  from  man  to  man  occurs  occasionally  by 
means  of  clothing,  but.  as  a  rule,  by  intimate  contact  with  the  diseased  skin, 
and  in  almost  <-\t'vy  case  by  sleeping  with  a  scabies  patient.  Among  the 
poorer  classes,  therefore,  a  scabies  patient  is  likely  soon  to  infect  the  entire 
family.     The  disease  is  often  spread  by  prostitutes. 

The  acarus  is  apt  to  attack  the  flexor  surfaces  of  the  joints  of  the  hand 
and  fingers,  the-  interdigital  folds,  the  lateral  surface-  of  the  fiiiLrcrs:  in  chil- 
dren with  a  delicate-  skin  the  palm  of  the  hand,  the  surroundings  of  the  elbow- 
joint,  tin-  anterior  axillary  fold:  and  in  women  the  nipple.  The  navel,  the 
skin  of  the  penis  and  scrotum,  the  trochanter  region,  the  flexor  of  the  knee 
and  the  internal  border  of  the  foot  are  attacked.  The  acarus  also  prefers  all 
those  portions  of  the  body  upon  which  the  underclothing  i-  tight.  The  face 
and  hairy  scalp  are  rarely  attacked.  Sämisch  has  described  a  case  in  which 
scabies  gave  rise  to  severe  inflammation  of  the. eyes  ("keratitis,"  "  Büschel- 
form  "'). 

The  irritation  from  the  itching  which  the  parasite  produces  by  its  burrow- 
ing in  the  -kin  i-  xcvy  acute,  especially  at  night,  for  at  this  time,  stimulated 
by  the  warmth  of  the  bed.  the  mite  nourishes  it-elf.  The  affected  individual 
attempts  to  relieve  the  irritation  by  vigorous  scratching.  Not  only  are  the 
small  nodular  efflorescences  produced  by  the  parasites  irritated  by  this  scratch- 
ing, but,  in  addition,  new  papular  elevations  are  formed  at  the  exit  of  the  hair 
follicle-,  ami  -mall  ve-icle-  like  millet  seeds  with  purulent  contents.  Contin- 
ued scratching  causes  new  eruptions,  while  the  older  ones  are  torn  away,  and 
become  covered  with  striae-like  blood  crusts,  from  which  finally  ulcer-  covered 
with  eschars  develop.  Marked  pustular  eruption-  often  fellow  even  in  young 
people  and  eczema  develops  in  all  those  who  suffer  for  a  long  time  from  the 
disease.  The  diagnosis  of  Bcabies  may  readily  he  made  from  the  localiza- 
tion of  the  excoriations,  a-  eczema  upon  the  nipple,  upon  the  fohl  of  the  axilla, 
upon  the  penis,  etc. 

A  peculiar  picture  resembling  the  mange  of  animal-  i-  produced  by  scabies 
norvegica  -.  crustosa.  This  -how-  a  thick,  dirty-gray  induration  composed  of 
deposits  of  epidermis  upon  the  palm  of  the  hand,  en  the  -ole  of  the  foot,  "U 
the  elbows,   on   the   face  and   the   hairy  -calp.      The-e   induration-  contain    the 

parasites  and  their  ova  often  in  enormous  number-.  According  to  Fürsten- 
berg thi-  form  of  scabies  i-  due  to  the  -mailer  sarcoptes  scabiei  crustosae, 
Fürstenberg. 

The  disease  usually  develops  typically  in  one  and  a  half  to  three  months 


568  THE  ANIMAL  PARASITES  OF  MAN 

after  infection.  The  eczema  due  to  scratching  has  by  this  time  spread  over 
the  entire  body;  the  longer  the  disease  lasts  the  more  marked  it  becomes. 
Aside  from  the  irritation  and  the  loss  of  sleep  due  to  this,  no  further  symptoms 
arise. 

Spontaneous  recovery  does  not  result,  but  recovery  from  scabies  in  the 
course  of  concurrent  febrile  diseases  is  noted  as  the  consequence  of  the  death 
of  the  parasite.  The  ova,  however,  do  not  always  die.  Therefore,  after  recov- 
ery from  the  disease,  the  itch  frequently  reappears. 

The  diagnosis  is  easy.  The  location  of  the  efflorescences  is  particularly 
characteristic.  We  can  hardly  err  in  making  a  diagnosis  of  the  itch  when 
a  markedly  itching  cutaneous  eruption  is  characterized  by  the  presence  of 
isolated  nodules,  particularly  upon  the  anterior  surface  of  the  trunk  and  ex- 
tremities, of  small  vesicles  upon  the  fingers  and  interdigital  folds,  in  the  palm 
of  the  hand  and  on  the  sole  of  the  foot,  with  pustules  upon  the  fingers,  espe- 
cially in  young  people,  in  whom  eczema  shows  itself  chiefly  in  those  areas 
between  the  nipple  and  the  knees  for  which  the  parasite  shows  a  preference. 
The  diagnosis  becomes  certain  by  the  discovery  of  the  acarus  grooves,  or  of 
the  parasite  itself.     In  all  doubtful  cases  microscopic  investigation  is  necessary. 

Prurigo  and  scabies  are  often  confounded.  Leaving  out  of  consideration 
the  time  and  place  of  development  of  the  first  prurigo  efflorescences,  prurigo 
differs  essentially  by  the  localization  of  the  eruption.  This  is  found  chiefly 
upon  the  lower  extremities,  especially  upon  the  extensor  surfaces  of  the  trunk, 
but  never  upon  the  flexor  surfaces  of  the  joints. 

After  scabies  has  been  recognized  in  an  individual,  it  is  wise  to  examine 
carefully  all  other  members  of  the  family,  and  to  treat  simultaneously  all 
who  are  affected.  The  aim  is  to  kill  the  parasite  and  heal  the  eczema.  In 
former  times,  when  the  parasitic  nature  of  the  itch  was  not  yet  understood, 
the  disease  was  looked  upon  as  almost  incurable;  we  can  to-day  rapidly  cure 
the  affection  by  a  number  of  remedies  such  as  sulphur,  tar,  naphthol,  balsam 
of  Peru,  styrax,  petroleum,  etc. 

It  is  sufficient  to  mention  a  few  among  the  great  number  of  prescriptions : 

T^   Florum   sulphuris,  )  __  90  „ 

Olei  f  agi,  f  ' ' 

Saponis  viridis,        j  _  _ 40  0 

Axungiae  poremaB,    ) 

Cretas  albas 15.0 

or  ty   Styracis  liquidi,      )   ._  20  0 

Florum  sulphuris,  ) 

Saponis  viridis 40.0 

Vaselini, 
Cretae  albae, 


l  ää 10.0 


or                 ^  /3-Naphtholi,  )_.^  100 
Creta?  albae,     ) 

Saponis  viridis 50.0 

Axungiaa  porcinas 100.0 


ARTHROPODA  569 

or  I£  Styracis  liquidi 35.0 

Spiritus  vini 10.0 

Olei   olivarum 65.1 1 

When  there  is  no  eczema  the  best  results  will  be  obtained  with  inunctions 
of  balsam  of  Peru.  The  patient  takes  a  bath  in  which  he  rubs  himself  briskly 
with  green  soap.  After  an  hour,  when  the  skin  has  become  entirely  dry. 
balsam  of  Peru  is  rubbed  into  the  entire  surface  of  the  body.  About  ten  gram- 
are  sufficient  for  this  purpose.  The  next  day  the  same  process  is  repeated. 
After  forty-eight  hours  the  patient  takes  another  bath,  which  completes  the 
proce--. 

In  the  majority  of  cases  it  is  well  to  give  a  bath  to  soften  the  epidermis 
before  beginning  the  actual  treatment.  In  private  practice  I  prefer,  as  a  rein- 
ed v  for  scabies,  the  above-mentioned  naphthol  salve,  which  or  the  fir-t  day  i- 
twice  rubbed  into  the  body  and  completely  allays  the  itching  during  'be  suc- 

C h'ng  night.     If  the  itching  should  return,  a  third  inunction  is  given  upon 

the  second  «lay.  The  patient  is  able  to  follow  his  ordinary  occupation.  It 
is  best  for  bim  to  wear  woolen  underwear  as  the  salve  will  less  readily  adhere 
to  tin-.  1'pon  the  sixth  day  a  bath  completes  the  antiscabies  treatment.  If 
there  is  eczema  this  necessitates  further  therapeutic  measures  upon  which  I 
cannot   here  enter. 

The  "rapid  cure-'"  were  formerly  much  in  vogue.  In  this  treatment  the 
patient  is  put  in  a  warm  bath  and  is  rubbed  with  black  30ap.  The  hath  should 
la-t  an  hour  and  a  half  and  be  followed  by  an  inunction  of 

I£   Sulphuris  citrini 10.0 

Potassae  subcarbonati 1." 

Axungiae I".(i 

This  finishes  the  treatment.  Sensitive  persons  readily  react  to  this,  a-  well 
as  to  other  rapid  cures,  by  an  eruption  of  eczema. 

Certain  forms  of  scabies  occur  in  various  domestic  and  wild  animals,  in 
the  horse,  the  sheep,  the  -oat.  the  camel,  the  llama,  the  pig.  the  dog.  the  fox 
and  the  lion.     These  parasites  occasionally  attack  man. 

According  to  Carron  du  Villards,  there  are  two  varieties  of  acarus  in  the 
Antilles  which  may  infect  the  eye.  Fischer  saw  a  decided  inflammation  of 
the  eye  produced  by  a  chicken  louse  (lipeurus  variabilis,  Nitzsch)  which  had 
found  it-  way  into  the  conjunctival  -ac  According  to  Megnin.  another  acarus. 
the  holothyrua  coccinella,  Gervais,  produces  in  bird-  a  dangerous  disease, 
which,  when  transmitted  to  man.  causes  itching  of  the  -kin  and  inflammation. 
Another  acarus,  called  by  the  inhabitants  of  the  Antilles  the  arador,  burrows 
into  the  akin  of  the  eyelids,  forming  brown,  tortuous  furrow-  which  may  he 
recognized  with  the  naked  eve.     it-  presence  produces  severe  itching. 

An  acarus   nephrophages  sanguinarius  ha-  been    found   by   Miyake  and 

Scriha  in  the  hemorrhagic  urine  of  a  Japanese.  Bow  important  this  acarus, 
which   i-  -aid   mo-1  closely  to  resemble  the  dermatocopteT  communis,  may  be, 

cannot  at  present  lie  determined.    The  significance  of  the 
Demodex  folliculorum,  Simon.  L842, 


570  THE   ANIMAL   PARASITES   OF  MAN 

is  still  debated.  This  acarus  lives  in  the  hair  follicles  in  comedones  and  in 
the  glands  of  Meibomius  in  the  skin  of  the  face  of  man.  In  the  dog,  the  pig, 
the  cat,  and  in  cattle,  hair  follicle  acari  have  been  observed  and  are  said  to  be 
varieties  of  the  parasite  of  man.  The  views  of  authors  are  divided  as  to  the 
importance  of  this  parasite  as  a  causative  agent  of  disease.  We  incline  more 
and  more  to  the  opinion  that  it  is  one  of  the  harmless  parasites,  and  that  its 
occurrence  in  acne  pustules  is  of  no  pathogenic  significance.  Nevertheless, 
it  is  found  with  extraordinary  frequency — according  to  Hunsche  even  in  92.5 
per  cent. — in  the  sebaceous  glands  of  perfectly  healthy  individuals.  The  clin- 
ical conception  formulated  by  Eaelmann  of  blepharitis  acarica  can  no  longer 
be  maintained.  The  acarus  is  found  with  great  regularity  in  the  ciliary  folli- 
cles of  normal,  as  well  as  of  abnormal, -eyelids. 

Of  the  linguatula,  or  tongue  worms,  which  are  elongated,  vermiform,  flat- 
tened or  cylindrically  curled  worms  whose  head  is  armed  with  an  elliptical 
chitin  mouth  and  two  retractile  claws,  one  is  parasitic  in  man.     This  is  the 

Pentastoma  tcenioides,  Budolphi,  1810. 

The  sexually  mature  parasite  lives  in  the  nasal  cavity,  the  forehead  bones 
and  jaw  of  the  dog,  the  wolf,  the  horse,  the  mule,  the  goat,  and,  occasionally,  also 
in  man.  The  eggs  discharged  with  the  nasal  mucus  contain  embryos  which 
reach  the  open  air  where  they  are  taken  up  by  such  animals  as  rabbits,  hares, 
cattle,  horses,  etc.,  and  also  sometimes  by  man.  They  penetrate  the  intestinal 
wall,  and  reach  the  liver  where  they  become  encysted.  For  a  long  time  the 
larva  pentastoma  denticulatum,  Kudolphi,  was  taken  for  an  independent  para- 
site. After  a  certain  time  the  larvae  may  wander  further,  and  in  this  way 
reach  the  respiratory  tract,  especially  the  nose.  In  other  cases  infected  organs 
are  eaten  by  Carnivora.  The  larvae  which  reach  the  intestinal  tract  finally 
find  their  way  to  their  preferred  points  of  lodgment.  Man  unquestionably 
infects  himself  in  a  similar  manner.  The  pentastoma  either  accidentally 
reaches  the  nose  or  is  introduced  into  the  intestinal  canal  by  contaminated 
food. 

The  sexually  mature  form  is  rarely  met  with  in  man.  Laudon  found  the 
parasite  in  a  locksmith,  who  suffered  for  years  from  jaundice  and  gastric  dis- 
turbance, and  later  from  epistaxis.  Usually  the  larva  (the  pentastoma  den- 
ticulatum ) ,  when  observed  in  man,  is  found  particularly  in  the  liver,  the  lung, 
the  spleen  and  small  intestine,  the  peritoneum,  the  heart  muscle  and  the 
kidneys.  Special  symptoms  are  not  present  in  these  cases.  The  pentas- 
toma can  be  diagnosticated  only  when  they  give  rise  to  irritative  symptoms 
in  the  nose  or  its  auxiliary  cavities  or  when  their  ova  are  found  in  the 
nasal  secretion. 

Pruner  was  the  first  to  find  in  the  liver  of  two  negroes  the 

Pentastoma  constrictum,  v.  Siebold,  1852. 

Observations  regarding  the  occurrence  of  this  parasite  are  very  scanty. 
It  appears  that  when  present  in  great  numbers  it  may  be  the  cause  of  fatal 
peritonitis. 


ARTHROPODA  571 

In  conclusion  I  must  mention  the 

INSECTS 

■which  are  parasitic  in  man.  and  I  should  first  like  to  consider  the  role  which 
they  play  in  the  transmission  of  infectious  diseases.  The  reports  concerning 
this  are  scanty  and  widely  scattered. 

From  the  interesting  investigations  of  Xutall  it  appears  that  it  is  only 
rarely  that  anthrax,  chicken  cholera  and  mouse  septicemia  are  transmitted  by 
bed-bugs  and  fleas,  probably  because  the  insects  which  absorb  the  microorgan- 
isms with  their  sting,  soon  rid  themselves  of  them.  It  cannot,  however,  be 
denied  that  by  crashing  the  sucking  animals  which  contain  these  microorgan- 
isms in  their  blood,  and  by  scratching  at  the  point  of  the  bite,  these  germs  may 
be  conveyed  to  man.  But  it  must  be  remembered  that  the  infection-  germs 
which  are  present  in  the  dejecta  of  bed-bugs  and  fleas  lose  their  toxic  proper- 
ties very  rapidly.     This  is  especially  noticeable  in  flea-. 

Plague  bacilli,  transmitted  to  bed-bugs  and  fleas,  appear  to  die  in  the 
intestinal  canal  of  these  insects.  The  danger  lies  in  the  fact  that  if  any  one 
crashes  an  insect  thus  infected,  and  the  bite  is  then  rubbed  or  scratched,  the 
bacilli  may  be  transmitted.  It  is  certain  from  the  experiments  or  Simmond 
that  flies  which  have  fed  upon  the  dejecta  or  the  bodies  of  cholera  patients  take 
up  cholera  germ-,  and  transmit  them  to  food.  Relapsing  fever  spirilli  taken 
into  the  intestine  of  bed-bugs  appear  to  die  with  relative  rapidity.  The  imme- 
diate inoculation  of  apes  with  bed-bugs  that  have  sucked  themselves  full  ami 
have  been  crushed,  ha-  been  followed  by  positive  results.  Typhoid  bacilli  may 
apparently  be  carried  by  flies.  It  has  been  further  proven  that  flies  may  take 
tubercle  bacilli  into  the  intestinal  tract.  The  bacilli  have  been  found  in  the 
dejecta  (fly  -peck-)  apon  walls,  in  closets,  ami  on  doors.  It  i-  not  unlikely 
that  in  regions  where  leprosy  exists  it  is  transmitted  by  mean-  of  sarcoptes. 
The  bubo  disease,  Egyptian  ophthalmia,  and  conjunctivitis  blennorrhoica  may 
be  transmitted  by  flic-.  Favus  and  impetigo  are  said  to  be  transmitted  by  lice. 
That  infection-  diseases  are  transmitted  to  man  by  mean-  of  the  Ixodes  is  more 
than  doubtful.  The  röle  played  by  the  ixodes  bovis,  Riley,  1869,  or  the  boöph- 
ilus  bovis,  Curtis,  1890,  and  by  the  tsetse  fly  in  Texas  fever,  the  tsetse  fly 
di-ea-e.  ha-  not  come  within  the  range  <>f  our  observation. 

Of  the  parasitic  insects  I  shall  only  refer  briefly  to  the  head  loose  (pedicu- 
lus  capitis,  de  Geer).  This  parasite  is  distributed  over  the  entire  world.  It 
generally  lives  upon  the  hairy  scalp,  but  in  cases  of  greal  uncleanliness  also 
infects  other  parts  of  the  body.     The  ova  of  the  bead  loose  are  rarely  found 

in  the  cilia.  From  the  excrement  of  the  lice  which  is  conveyed  to  the  con- 
junctival -ac  by  the  hand-,  conjunctivitis  ami  blepharitis  may  apparently  he 
produced.  In  cases  of  stubborn  head  eczema,  especially  in  children,  the  p 
ence  of  lice  should  invariably  he  looked  for.  It  i-  known  that  plica  polonica 
usually  develops  from  a  preceding  pediculosis  capitis  with  accompanying 
eczema.  The  plica  polonica  (Polish  plait)  mu-f  be  removed  with  the  scissors. 
To  exterminate  lice,  washings  with  vinegar,  petroleom,  or  corrosive  sublimate 
(1-1,000)  ami  combing  the  hair  by  mean-  of  a  tine  comb  are  advisable.    The 

scalp  should  then  he  painted   twice  daily  with  Xictl-La--ar  zinnoher  -al\e: 


572  THE  ANIMAL  PARASITES  OF  MAN 

I£  Hydrargyri  sulfurati  rubri 1.0 

Sulfuris  sublimati 24.0 

Olei  bergamottae gtt.  xxv 

Vaselini  flavi,  ad 100 

In  children,  Joseph  advises : 

^   Acidi  salicylici 1.0 

Tincturae  benzoes 2.0 

Vaselini  flavi,  ad 50.0 

to  be  rubbed  into  the  scalp  twice  daily. 

The  clothes  louse,  pediculus  vestimenti,  Burmeister,  lives  upon  the  throat, 
neck,  and  trunk  of  man.  The  eggs  are  deposited  in  the  lanugo  hair  of  the 
skin,  as  well  as  in  the  underclothing.  The  bite  of  the  louse  causes  severe 
itching,  and  by  scratching  striae-like  wounds  are  produced.  If  the  condition 
exists  for  a  long  time,  open  wounds  and  ulcers  of  various  kinds  appear,  and 
finally  a  permanent  pigmentation  of  the  skin  which  is  particularly  noticeable 
in  those  areas  in  which  the  clothes  are  worn  close  to  the  body.  So-called  lousi- 
ness is  produced  by  the  abundance  of  the  clothes  louse.  Cleansing  the  clothes 
and  disinfecting  the  same,  and  washing  the  body  with  vinegar  or  petroleum 
will  rapidly  remove  the  disease. 

The  body  louse  (phthirius  inguinalis,  Kedi,  1668)  is  most  frequently  found 
in  the  hair  surrounding  the  pubes.  Thence  it  is  distributed  over  the  trunk 
to  the  axillary  cavity,  into  the  beard,  into  the  cilia  and  into  the  eye-brows, 
but  is  very  rarely  found  upon  the  hairy  scalp.  The  exanthem  produced  by 
scratching  is  usually  found  in  corresponding  places.  The  maculae  caerulea?, 
composed  of  reddish  brown  flakes,  which  are  found  upon  the  anterior  lateral 
aspect  of  the  thorax,  on  the  upper  thighs  and  buttocks,  are  of  a  peculiar  char- 
acter, and  are  probably  produced  by  a  poison  contained  in  the  salivary  gland. 
The  parasite  may  be  removed  by  inunctions  of  gray  salve  followed  by  a  bath. 
Inunctions  with  balsam  of  Peru  or  white  precipitate  salve  will  also  rapidly 
remove  the  parasites.  The  phenomena  produced  by  bed-bugs  (cimex  lectu- 
larius,  Merrett,  1667,  cimex  ciliatus,  Eversmann,  1811,  cimex  rotundatus,  Sig- 
noret,  1851)  and  those  produced  by  the  flea,  pulex  irritans,  Linne,  1758,  are 
sufficiently  well  known. 

The  sand-flea  (sarcopsylla  penetrans,  Linne,  1758)  has  lately  become  of 
more  interest  to  Germany  on  account  of  its  appearance  in  the  colonies.  Carried 
from  its  home  in  South  America  to  West  Africa,  the  parasite  has  gradually 
spread  itself  from  west  to  east,  until  it  reached  German  East  Africa.  By 
1897  it  became  a  land  plague  in  Uhehe. 

After  the  female  (the  male  lives  independently)  has  bored  its  way  under 
the  toe-nail,  it  appears  on  the  first  day  as  a  small  harmless  point,  and  may 
easily  be  removed  without  pain.  Early  removal  is  the  only  protection  from 
serious  consequences ;  it  is  therefore  advisable  to  inspect  the  feet  daily,  and  this 
is  the  more  necessary  in  infected  regions,  as  the  sand-flea  at  first  causes  no 
symptoms. 


ARTHROPODA 


573 


In  eight  to  fourteen  days  the  posterior  portion  of  the  abdomen  of  the  para- 
site swells  to  the  size  of  a  pea.  It  contains  from  GO  to  100  eggs.  After  depos- 
iting the  eggs  the  parasite  dies.  By  incautious  manipulation  in  its  removal, 
or  by  other  trauma  which  affect  the  toes  and  cause  the  abdomen  of  the  para- 


Fig.  57. — Sarcopsylla  Penetrans,  Band- 
plea,  Prior  t<>  its  Entrance  Under  the 
Nail  of  the  Toe. 


I'm;.  58. — Sarcopsylla  Peneth  ins,  Removed 
from  a  Wound  of  the  Nail. 


site  to  rupture,  the  ova  are  liberated,  and  stubborn  ulcers  develop  which,  if 
neglected,  cause  the  Loss  of  the  toes.  Wound  infection  not  rarely  complicates 
the  further  course.  The  parasite  should  be  removed  by  carefully  Lifting  it 
out  with  a  dull  forceps. 

FLY    LARVAE   (Maggots) 

Ply  larvae  are  occasionally  observed  as  parasites  in  man.  The  mother  ani- 
mals belong  to  the  family  of  oestrides  or  of  the  muscides,  the  actual  flies.  The 
clinical  picture  produced  by  Larvas  is  known  as  myiosis  externa  or  interna  3. 
intestinalis. 

In  Europe  myiosis  externa  is  mostly  produced  by  the  Larva  of  the  muscides, 
more  rarely  by  the  Larva  of  oestrides.  For  the  Latter  the  larva  of  the  hypo- 
derma  bovis,  de  Geer,  or  hypoderma  diana,  Brauer,  are  responsible.  In  the 
tropics  the  gadfly  boil  of  man  is  due  to  the  dermatobia  noxialis,  Brauer,  or  the 
ochromyia  anthropophaga.  As  boob  as  the  eggs  of  these  flies  have  been  depos- 
ited upon  the  skin,  the  Larvas  pour  forth,  bore  into  the  skin,  and  in  the  course 
of  a  few  months  cause  the  affection  which  is  known  as  the  "gadfly  boil  "  of 
entile,  of  the  Btag  and  of  the  roe.  In  cattle  Larvae  are  taken  up  by  the  mouth 
and  finally  find  their  way  under  the  skin:  whether  the  Bame  course  is  followed 
in  man  has  Qoi  vet  been  proven.  Recovery  occurs  spontaneously,  by  the 
egress  of  the  parasites,  or  by  Burgical  opening  and  extraction  of  the  larva« 
from  the  carbuncle-like  cutaneous  swelling.  Erautner  observed  a  dipteren 
larva  in  an  isolated  Location.     He  extracted  a  larva  of  the  hypoderma  bovis 

from   the  anterior  (handier  of  the  eye. 

The  occurrence  of  oestrus  larva'  in  the  digestive  apparatus  of  man  ha 


574  THE  ANIMAL  PARASITES  OF  MAN 

yet  been  determined  with  certainty.  Some  authors,  however  have  thought 
that  they  produce  another  disease,  the  "  creeping  disease." 

In  the  hol  summer  months  it  is  noticed — the  number  of  cases  observed  is 
still  limited — that  upon  the  uncovered  portions  of  the  body  irregular,  serpen- 
tine, linear  elevations  appear,  which  never  branch,  and  these  give  rise  to  itching 
and  burning,  and  cause  a  red  elevation,  slightly  raised  above  the  skin.  The 
line  is  elongated,  and  tapers  rapidly  to  a  point  (1-15  cm.  in  twenty-four 
hours).  Occasionally  at  intervals  of  from  1-2  cm.  small  nodules  are  notice- 
able, which  have  been  declared  to  be  the  fecal  mass  discharged  by  this  insect. 
That  the  disease  is  caused  by  an  animal  parasite  is  certain.  The  parasite  itself, 
which  has  been  thought  to  be  a  gastrophilus  larva,  has  not  yet  been  zoologically 
and  definitely  determined. 

The  majority  of  affections  of  myiosis  externa  are  caused  by  muscides 
larvae.  In  Europe  it  is  particularly  the  sarcophila  Wohlfart,  Portschinskv, 
1875,  in  America  the  lucilia  macellaria,  Fabricius,  1791.  Those  persons  are 
most  endangered  who  sleep  in  the  open  air  and  who  suffer  from  any  purulent 
process:  Pus  from  the  ear,  nose,  or  similar  affections.  The  fly  is  otherwise 
extremely  timid  and  never  enters  living  rooms,  but  is  attracted  by  pus  and 
deposits  its  eggs.  The  larva?,  which  soon  come  forth,  cause  remarkable  de- 
struction by  their  enormous  appetite.  Entering  the  auditory  passages,  they 
eat  the  external  covering,  penetrate  the  tympanic  cavity,  and  pass  through 
the  Eustachian  tube  into  the  pharynx.  Great  destruction  is  wrought  in 
the  nose  and  its  auxiliary  cavities,  where  ulcers  and  purulent  wounds  are 
produced.  Autopsy  findings  confirm  the  extraordinary  virulence  of  these 
parasites. 

In  the  conjunctiva,  in  the  oral  cavity,  even  in  the  urethra  and  the  bladder, 
maggots  have  occasionally  been  observed.  Formerly,  before  the  introduction  of 
antiseptic  surgery,  maggots  in  wounds  were  not  very  uncommon;  to-day  they 
appear  only  in  such  as  are  grossly  neglected.  Besides  the  parasites  mentioned 
above,  in  man  larvae  of  calliphora  vomitoria  Robineau-Desvoidy,  cimex  limen- 
sis,  sarcophaga  carnaria,  Meigen,  musca  cadaverina,  musca  domestica,  musca 
stabulans,  and  others  have  been  observed. 

I  should  like  to  say  here  that  numerous  occasional  parasites,  such  as  gal- 
leria  mellonella,  dermestes  lardarius,  geophilus  sodalis,  geophilus  hortensis, 
thousand-leggers,  have  been  removed  by  physicians  from  the  nose.  Laboulbene 
mentions  a  case  in  which  the  gammarus  pulex  was  vomited.  This  by  no  means 
exhausts  the  number  of  the  occasional  parasites. 

For  their  removal,  corrosive  sublimate  injections  and  chloroform  or  turpen- 
tine mixtures  are  advised. 

The  myiosis  intestinalis  is  a  much-debated  parasite.  Although  numerous 
well-observed  cases  of  this  kind  are  on  record,  the  presence  of  the  larvae  of  flies 
in  the  digestive  apparatus  is  still  doubted.  We  shall  touch  lightly  on  these 
doubts  which  are  nowise  justified.  Those  that  have  been  observed  up  to  now 
are  the  larva  of  musca  vomitoria,  musca  domestica,  musca  nigra,  musca  cor- 
vina,  musca  pendula,  musca  meteorica,  calobata  cibaria,  hydrothorea  meteorica, 
sarcophaga  affmis,  sarcophaga  carnaria,  sarcophaga  haemorrhoidalis,  sarcoph- 
aga haematodes,  anthomyia  canicularis,  anthomyia  scalaris,  etc. 


ARTHROPODA  575 

On  account  of  the  myriads  of  flies  about  our  houses  an<l  their  habit  of 
resting  preferably  upon  food  where  they  deposil  their  eggs  and  on  account  of 
the  great  production  of  fly  Larvae  in  water,  it  is  quite  remarkable  thai  larva' 
of  flies  do  not  more  frequently  reach  the  gastro-intestinal  canal  of  man.  There 
are  many  avenue-  by  which  the  larva?  of  the  anthomyia  varieties  which  de- 
posit their  ova  in  salad,  radishes,  berries,  etc.,  may  reach  the  intestinal  canal. 
.Many  of  the  larva'  are  destroyed  in  the  digestive  tract,  or  do  not  find  the  condi- 
tions suitable  for  their  existence,  but  they  generally  possess  such  extraordinary 
resistance  as  to  be  able  to  withstand  the  digestive  process. 

There  is  no  specific  symptomatology.  In  the  history  of  these  patients 
complaints  of  nausea,  tendency  to  vomit.  TOmiting,  sour  eructations,  more  or 
less  severe  pain  in  the  epigastrium,  and  attacks  of  colic  may  appear.  At  one 
time  there  is  constipation,  at  another  time  diarrhea,  with  or  without  blood. 
8  ere  spasmodic  attacks,  cramps,  sensations  of  fear  are  observed,  which  cease 
at  once  when  the  larvae  are  passed.  There  are  no  sequels,  however,  as  the  ex- 
istence of  the  parasite  is  so  brief.  The  Larvae  are  voided  per  anum  with  the 
stools  or  by  the  mouth  in  vomitus;  sometimes  more  than  one  hundred  larva? 
are  discharged. 

As  soon  as  the  discharge  of  larva'  has  been  recognized,  an  attempt  should 
be  made  by  therapeutic  measures  to  effeel  the  speedy  removal  of  the  parasite. 
If  the  larvae  are  still  present  chiefly  in  the  stomach,  they  may  be  removed 
by  lavage.  In  naphtholin  (0.5-1.0  in  single  doses,  up  to  5.0  as  a  daily  dose 
lor  adult-)  we  no  doiil.t  possess  a  remedy  which  causes  the  death  of  the  larva?, 
that  is,  brings  about  their  rapid  removal. 

I'.<  sides  those  mentioned,  there  are  a  number  of  other  insects  which  are  "  oc- 
casional" parasites  of  man.  I  need  mention  here  only  the  differenl  varieties 
of  Hies,  mosquitoes,  wasps,  bees,  hornets,  etc..  which  occasionally  attack  man. 
and  by  their  sting  cause  marked  pain.  G.  Braun  has  lately  reported  the  bite  of 
poisonous  spiders  (Latodectus  Lagubris)  which  may  bring  about  serious  symp- 
toms. The  bite  of  tin-  tarantula  is  harmless,  but  that  of  scorpions  causes 
re  inflammatory  cutaneous  symptoms.  In  conclusion,  it  musl  hi'  men- 
tioned that  various  caterpillars  supplied  with  hairs  containing  retroserrates 
and  spinules  may  cause  severe  irritative  phenomena  upon  the  skin,  the  con- 
nective tissue,  the  corium  and  iris.  Cray  or  grayish  yellow  nodules  the  siZt> 
of  a  lentil,  being  round  or  oval,  form  in  the  [ris  and  subconjunctival  cellular 
tissue.  Laudon  mention-  that  in  girls  inflammation  of  the  sexual  apparatus, 
swelling  of  the  Labia  and  Leukorrhea  may  he  caused  by  the  hair-  of  caterpillars. 
;1nd  also  that  the  toxic  substances  contained  in  the  cavities  of  the  hair-  of 
caterpillars  may,  by  penetrating  or  tearing  the  human  skin,  produce  Bevere 
irritative  phenomena. 

For  the  relief  of  tin-  bites  or  -tim_r-  of  insects,  painting  with  sal  am- 
moniac, ichthyol,  or  ichthyo]  Balve  or  the  application  of  Lchthyol  plaster,  ia 
ad\  ised. 

The  severe  affections  of  the  eye  produced  by  the  hair-  of  caterpillars  re- 
quire the  extraction   of  the  hairs   which   have  entered;   in    iritis,   atropin   and 

warm  compresses.     Unfortunately,  the  prognosis  is  not  favorable.     The  cuta- 
neous irritation  may  he  Lessened  by  raaelii]  or  inunctions  with  lanolin. 


576  THE  ANIMAL  PARASITES  OF  MAN 


LITERATURE 

R.  Leuckart:  "Die  Parasiten  des  Menschen,"  II.  Aufl.,  Leipzig,  1886-91. 

Braun:  "Die  thierischen  Parasiten  des  Menschen,"  IL  Aufl.,  Würzburg,  1895. 

Huber:  "Bibliographie  der  klinischen  Helminthologie,"  Jena. 

Mosler  und  Peiper:  "Thierische  Parasiten."   "Nothnagels  specielle  Path.  u.  Ther.," 

VI.  Bd.,  Wien,  1894. 
E.  Peiper:    Ergebnisse    der    allgemeinen    Pathologie    und    pathologischen    Anatomie, 

III.  Jahrg.     "Thierische  Parasiten  des  Menschen." 
E.  Peiper:  "Die  Verbreitung  der  Echinokokkenkrankheit  in  Vorpommern,"  Stuttgart, 

1894. 
E.  Peiper:  "Fliegenlarven  als  gelegentliche  Parasiten  des  Menschen,"  Berlin,  1900. 


TOXICOLOGY 


88 


IMPORTANT   POISONS  AND   THEIR   TREATMENT 

By    R.    v.    JAKSCH,  Prague 

It  is  a  difficult  undertaking  to  confine  within  the  limits  of  an  article  all 
the  data  of  importance  in  the  study  of  the  poisons  with  which  the  practising 
physician  is  likely  to  come  into  contact. 

In  modern  clinical  medicine,  the  conception  of  poisoning  must  be  very 
widely  extended.  The  amount  of  material  to  be  considered  is  enormous,  be- 
cause every  pathogenic  agent  which  finds  entrance  into  the  human  organism, 
including  also  every  contagium  vivum,  may  produce  toxic  action.  This  great 
group  of  poisons,  the  endogenous  toxicoses,  we  shall  not  here  consider,  but 
shall  content  ourselves  with  the  discussion  of  the  exogenous  toxicoses  which 
are  most  important  to  the  physician. 

In  the  definition  of  the  word  poison,  we  are  at  once  confronted  with  ditli- 
culties  which  need  not  be  further  dwelt  upon.  Our  object  is  to  consider  a 
number  of  symptoms;  and  the  treatment  of  a  series  of  diseases  all  of  which 
are  due  to  the  introduction  within  the  body  of  certain  well-known  chemical 
agents  from  without.  These  agents  include  the  acids,  the  alkalies,  the  metal- 
loids, the  metallic  salts,  gases,  bodies  that  belong  to  organic  chemistry,  such 
as  ihc  fat  derivatives,  bodies  of  the  aromatic  group,  the  camphors  ami  balsams, 
the  alkaloids,  the  glucosides,  bitter  and  indifferenl  bodies,  the  toxalbumins 
and,  finally,  vegetable  and  animal  poisons,  the  composition  of  which  is  only 
partially  known  to  us. 

from  this  almosl  endless  series  it  is  apparent  that  we  cannot  describe  all 
of  tin'  pathologic  pictures  produced  by  these  poisons,  hut  it  will  he  our  objeel 
to  take,  as  an  example,  an  important  representative  of  each  of  the  previously 
mentioned  groups,  and  describe  its  effects. 

We  will  first  direct  our  attention  to  the  acids.  The  pathologic  processes 
produced  by  these  poisons  may  very  properly  he  designated  as  acidosis.  Tin1 
differences  between  these  acids  und  in  their  composition,  if  we  include  the 
organic  ami  inorganic  varieties,  are  parallel  with  the  difference  in  the  clinical 
picture  which  develops  after  their  introduction  into  the  human  organism. 
A-  the  type  of  acidosis,  I  -hall  consider  inorganic  acid,  sulphuric  acid,  anil 
shall  discuss  the  Important  symptoms  of  this  poison  as  acidosis.  I  may  re- 
mark  that    I   choose  this  particular  acid    for  the  reason  that    this  acid   toxio 

is  observed  with  relative  frequency  by  the  physician. 

There  can  he  no  douhl  that  by  the  introduction  of  large  amounts  of  acids, 
nervous  symptoms  may  he  produced;  hut  symptoms  "f  tin-  kind  are  rarely 
observed  at  the  bedside,  as  the  local  symptoms  produced  by  the  acid  toxicosis 

579 


580  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

completely  dominate  the  scene.  Those  acids  whose  corrosive  effects  are  less 
prominent,  as,  for  example,  hydrochloric  acid,  may  show  nervous  symptoms 
which  can  be  referred  to  the  acid,  but  even  this  is  relatively  rare.  If  an  indi- 
vidual takes  large  quantities  of  free  acid,  e.  g.,  sulphuric  acid,  what  symptoms 
are  produced?  The  deeply  invading  eschars  which  cover  all  parts  of  the 
mucous  membrane  are  characteristic,  particularly  in  those  areas  which  are 
brought  in  contact  with  the  acid  in  deglutition.  Severe  retching  and  the 
vomiting  of  brown  pulpy  masses,  excessive  pain  in  the  gastric  region,  intense 
burning  in  the  esophagus,  and  marked  salivation,  are  the  immediate  conse- 
quences of  such  a  toxicosis.  The  vomited  material  has  an  acid  reaction; 
within  a  few  hours  the  symptoms  of  marked  renal  irritation  develop. 

If  the  amount  of  acid  which  has  reached  the  stomach  is  relatively  large, 
and  the  acid  is  concentrated  with  the  continuance  of  vomiting,  symptoms  of 
perforative  peritonitis  soon  appear,  due  to  the  erosion  of  the  walls  of  the  stom- 
ach by  the  acid,  and  the  patient  succumbs  in  a  short  time,  often  within  a  few 
hours.  But  even  if  the  amount  of  acid  swallowed  was  not  large,  days,  even 
weeks,  must  elapse  before  the  eschars  heal.  Dysphagia,  salivation,  pain  on 
deglutition  continue,  and  often  fever  follows,  the  wounds  which  have  been 
produced  by  the  acid  becoming  the  point  of  entrance  by  which  pyogenic  organ- 
isms find  their  way  into  the  body.  An  important  fact  is  that  all  poisonings 
with  corrosive  acids,  even  in  cases  which  apparently  run  a  mild  course,  may 
lead  to  stricture  of  the  esophagus;  indeed  this  is  an  almost  invariable  result. 
Of  course  the  frequency  of  stricture  depends  on  the  variety  of  the  acid.  Poi- 
soning by  sulphuric  acid  almost  always  produces  this  symptom,  nitric  acid 
less  frequently,  hydrochloric  acid  relatively  seldom,  but  there  can  be  no  doubt 
that  strictures  also  occur  from  hydrochloric  acid  toxicosis.  They  are  less  often 
seen  after  poisoning  with  organic  acids,  such  as  acetic  acid,  etc.,  perhaps  be- 
cause poisoning  with  concentrated  solution  of  these  acids  is  relatively  rare. 

An  important  symptom  which  must  be  discussed  is  renal  irritation  caused 
by  acid  toxicosis,  which,  in  my  experience,  often  leads  to  the  typical  signs  of 
acute  toxic  nephritis.  Acid  nephritis  may  occur  in  all  acid  toxicoses;  most 
frequently,  however,  we  meet  with  it  after  poisoning  with  sulphuric  acid. 
The  symptoms  are  exactly  the  same  as  in  acute  nephritis  due  to  other  causes, 
but  I  must  emphasize  the  fact  that  edema  does  not  accompany  this  form  of 
nephritis,  and,  furthermore,  that  dissolved  hemoglobin  frequently  appears  in 
the  urine. 

The  prognosis  in  poisoning  with  acids  should  always  be  considered  grave, 
as,  even  in  the  mildest  cases,  it  can  never  be  asserted  at  the  onset  that  stricture 
of  the  esophagus,  which  is  invariably  so  dangerous,  may  not  develop.  Even 
with  judicious  treatment,  stricture  may  result  in  under-nutrition,  or  in  actual 
starvation  with  all  its  consequences. 

In  regard  to  the  diagnosis,  the  fact  that  an  acid  toxicosis  is  present  may 
be  readily  determined  from  the  markedly  acid  composition  of  the  vomited 
material,  and  from  the  previously  described  eschars.  We  must  determine  with 
which  acid  we  are  dealing  by  a  testing  for  the  presence  of  that  acid  to  which 
the  pathologic  picture  points.  If,  for  example,  the  eschars  are  yellow  or  yel- 
lowish, it  may  be  presumed  that  nitric  acid -was  the  toxic  agent.     If  the  mucous 


ACIDS  581 

membrane  looks  as  though  it  had  been  scalded,  hydrochloric  acid  should  be 
thought  of;  deeply  invading,  leather-like  eschars  are  peculiar  to  sulphuric  acid 
toxicosis,  white  eschars  are  peculiar  to  tartaric  acid,  etc.  The  presence  of  the 
special  acids  must,  however,  be  proven  by  chemical  analysis,  the  consideration 
of  which  is  not  permissible  within  the  scope  of  this  article.  Examinations  of 
this  kind  should,  if  possible,  be  made  by  each  physician  for  himself.  But  we 
cannot  demand  thai  the  practising  physician  make  these  tests  for  himself  he- 
cause  complicated  chemical  apparatus  is  necessary,  and  therefore  I  limit  myself 
in  this  article  to  a  few  general  indications.  Certain  inorganic  acids,  such  as  sul- 
phuric acid  and  nitric  acid,  may  be  very  readily  determined;  the  proof  of  the 
presence  of  hydrochloric  acid  is  more  difficult,  since  it  is  normally  present  in 
all  stomach  contents.  But  in  most  cases  it  is  sufficient  to  demonstrate  by 
titration  with  an  alkali  a  large  amount  of  free  acid  in  the  vomited  material. 

Regarding  the  therapy,  our  sovereign  remedy  is  milk,  which  possesses  in  a 
high  degree  the  power  of  acid  neutralization;  if  this  is  not  immediately  at 
hand  (for  rapidity  of  action  is  the  most  important  and  first  requisite  in  the 
treatment  of  acid  toxicosis)  then  soap  suds  is  to  be  administered;  solutions 
of  albumin  are  also  advisable;  of  drugs  as  antidote-,  magnesia  usta  in  water 
is  advisable,  also  lime  water.  The  severe  pain  which  these  poisonings  cause 
justifies  the  use  of  opiates,  morphin  and  Cocain.  Unfortunately,  painting  the 
mucous  membranes  with  the  last-named  remedies  has  repeatedly  proved  disap- 
pointing to  me. 

Lavage  of  the  stomach  in  such  cases  necessitates  greai  care;  lavage  of  the 
stomach  in  poisoning  from  sulphuric  acid,  particularly,  involves  certain  dan- 
ger to  the  patient,  for  it  cannot  be  denied  that  by  such  a  process  a  gastric 
perforation  may  be  produced.  It  must  also  be  remembered  that  even  the  act 
of  washing  out  the  -tomach  in  such  patients  produces  severe  pain,  and  other 
forms  of  distress. 

I  musl  briefly  describe  those  acid  intoxications  which,  on  account  of  their 
not  infrequent  occurrence  and  their  clinical  picture,  occupy  a  special  position, 
and.  therefore,  have  certain  interest  for  the  physician.  These  are  poisoning 
by  oxalic  ami  prussic  acids. 

We  shall  first  describe  OXALIC  \<n>  toxicosis.  Oxalic  acid  itself,  above 
all  its  salts,  which  are  used  for  polishing  metal  ware,  and  to  remove  ink  -pots 
from  the  skin,  i-  in  common  ose,  and  is  a  frequent  cause  of  tin-  toxicosis. 

Oxalic  acid  and  it-  Baits  produce  like  mineral  acids  a  corrosive  effed  upon 
the  mucous  membranes  which  is  shortly  followed  by  a  considerable  reaction 
and  subsequent  inflammation  in  the  surrounding  area:  there  results  a  picture 
which  more  closely  resembles  poison  by  alkalies  than  by  acid-  (see  below ). 

The  nervous  symptoms  which  invariably  appear  in  the  course  of  poisoning 

from    this   acid.   Buch    a-  convulsions,    trismus,   and    tetanic    attack-,    are    quite 

noteworthy,    in  other  cases,  however,  rery  threatening  Bymptoms,  oliguria  and 

anuria,  become  prominent  a-  signs  of  severe  acute  toxic  renal   insufficiency 

due  to  infarction  of  the  kidney  with  calcium  oxalate. 

The  prognosis  in  tin-  form  of  poisoning  i-  always  Berious;  and  in  all  cases 
a  threatening  clinical  picture  results.  The  diagnosis  may  he  made  from  the 
symptom-  sketched  above,  and  i-  usually  easy.     It  becomes  certain,  however. 


582  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

only  when  it  is  possible  to  demonstrate  oxalic  acid  or  its  salts  in  the  excre- 
tions, above  all,  in  the  vomited  material.  In  cases  of  poisoning,  in  which  we 
have  the  relatively  slight  corrosive  effects  which  oxalic  acid  produces,  energetic 
gastric  lavage,  best  of  all  with  lime  water,  which  changes  oxalic  acid  and  its 
soluble  salts  into  insoluble  calcium  oxalate,  may  be  resorted  to;  lime  water 
may  also  be  given  internally.  The  use  of  sucrate  of  lime  has  been  especially 
praised. 

As  with  oxalic  acid  toxicosis,  a  special  position  has  been  assigned  to  poi- 
soning with  prussic  acid.  In  concentrated  solution  it  is  one  of  the  most  vio- 
lent poisons  known,  and  in  the  course  of  a  few  minutes  causes  death.  With 
a  loud  cry,  the  person  poisoned  collapses,  the  respiratory  frequency  rises  enor- 
mously, convulsions  occur,  and  in  a  few  minutes  death  results ;  so  rapid  is  the 
course  that  the  physician  rarely  has  an  opportunity  of  attempting  relief.  If 
there  is  time,  immediate  washing  out  of  the  stomach,  with  the  addition  of 
hydrogen  peroxid,  is,  at  all  events,  in  place;  subcutaneous  injections  of  atro- 
pin,  etc.,  have  been  advised,  but,  in  the  main,  we  are  compelled  to  say  that  in 
severe  cases  of  poisoning  therapy  is  ineffectual,  and  only  in  the  mild  cases  may 
we  count  upon  success. 

We  now  turn  to  the  second  group  of  poisons,  that  of  the  alkalies,  salts  of 
alkaline  metals,  and  metalloids.  We  shall  describe  only  three  forms  of  poi- 
soning, namely:  1,  Lye  toxicosis;  2,  poisoning  with  potassium  chlorate;  3,  poi- 
soning with  salts  of  barium. 

Next  to  poisoning  with  sulphuric  acid,  unquestionably  poisoning  with  lye 
is  undoubtedly  most  often  observed  by  the  physician.  We  never  get  poisoning 
by  pure  caustic  soda,  or  pure  caustic  potash,  but  with  mixtures  which  contain, 
besides  these  bodies,  potassium  carbonate  and  other  salts,  i.  e.,  with  fluids  which 
are  called  in  commerce  soda  solution  and  caustic  soda. 

What  symptoms  follow  the  introduction  of  these  substances  by  the  mouth  ? 

In  a  short  time  vomiting  of  glassy,  smeary,  soap-like  masses  occurs  and 
may  continue  for  hours,  or  even  days;  the  vomited  material  has  an  intensely 
alkaline  reaction,  and  later  often  assumes  a  brown  to  brownish-red  color  due 
to  decomposed  hemoglobin.  The  patient  is  tortured  by  great  pain,  particu- 
larly upon  deglutition,  the  areas  of  the  mucous  membrane  which  have  come  in 
contact  with  the  caustic  substance  appear  softened,  oozing,  swollen,  and  cov- 
ered with  pseudo-membranes  which  desquamate  in  a  few  days,  and  then  cause 
the  dreaded  formation  of  strictures,  particularly  in  the  esophagus.  Peritonitis, 
due  to  perforation  of  the  stomach  by  the  corrosive  action  of  the  alkali  upon 
its  walls,  may  also  appear.  The  result  of  poisoning  of  this  kind  is  always 
serious,  and  in  apparently  mild  cases  the  possible  sequel  of  stricture  of  the 
esophagus  renders  the  prognosis  unfavorable.  I  may  add  that  alkalies,  ceteris 
paribus,  give  rise  to  stricture  in  decidedly  slighter  concentration  than  acids. 

The  treatment  consists  in  the  immediate  neutralization  of  the  alkali,  which 
is  best  accomplished  by  a  lemonade  containing  tartaric  acid.  Prompt  gastric 
lavage  is  contraindieated  on  account  of  the  danger  of  perforation  of  the 
stomach;  on  the  other  hand,  on  account  of  the  severe  pain,  the  use  of  mor- 
phin and  other  opiates  will  be  necessary.  Cocain  has  here  been  as  ineffective 
as  in  the  treatment  of  acid  toxicosis. 


ALKALIES,  SALTS  OF  ALKALINE  METALS,  AND  METALLOIDS       583 

Of  special  importance  in  this  group  of  poisons  is  potassium  chlorate; 
hence  we  shall  briefly  consider  it.  The  drug  is  of  special  significance  for  the 
physician,  a-  poisoning  by  its  medicinal  use  has  been  frequently  observed  in 
the  Last  few  years.  The  quantity  of  the  salt  necessary  to  bring  about  this 
condition  varies  vry  widely  in  different  individuals.  The  lethal  dose  in  chil- 
dren is  from  5  to  6  grams  and  in  adults  15  grams  or  more. 

This  toxicosis  differs  particularly  from  poisoning  by  alkalies  in  that  there 
are  no  local  corrosive  effects. 

Such  patients,  however,  show  extreme  cyanosis,  they  complain  of  a  sense 
of  burning  and  oppression  in  the  chest,  the  skin  assume-  a  yellowish  hue, 
hemoglobin  (  hematin  )  appears  in  the  urine  without  any  other  sign  of  nephritis. 
In  the  further  course  of  the  affection  there  are  severe  nervous  symptoms,  such 
as  clonic  and  tonic  spasms  followed  by  delirium  and  then  by  deep  coma;  in 
this  condition  the  patient  succumbs.  Moreover,  there  are  undoubted  cases  of 
poisoning  in  which  the  typical  symptoms  of  acute  nephritis  appear,  and  the 
patient  dies  of  uremia. 

The  prognosis  is  always  dubious;  but  recovery  may  occur  even  in  the 
severesl  cases. 

The  diagnosis  is  made  more  certain  by  the  demonstration  of  methemoglobin 
in  the  blood,  and  proof  positive  is  the  presence  of  the  salt  in  the  fluid  obtained 
by  gastric  lavage.  If  the  amounts  introduced  were  very  large,  the  character- 
istic vapor-  of  chlorin  gas  are  at  once  given  off  upon  the  addition  of  hydro- 
chloric acid.  The  treatment  requires  immediate  and  thorough  washing  of  the 
stomach,  and  the  avoidance  of  the  introduction  of  acid-,  for  the  latter  generate 
in  the  stomach  a  very  dangerous  ehlorin  gas.  The  use  of  enemata  is  also  indi- 
cated to  eliminate  the  poison  which  perhaps  may  already  be  present  in  the 
lower  portions  of  the  intestine. 

A  few  words  in  regard  to  the  combinations  ok  baeium. 

All  of  the  soluble  -alts  of  barium  an'  very  poisonous!  Even  the  insoluble 
barium  carbonate  may  be  changed  in  the  stomach  into  the  soluble  barium 
chlorid,  and  then  have  a  toxic  effect. 

The  principal  symptoms  are:  Severe  pain  in  the  abdomen,  profuse  diar- 
rhea. Bigns  of  acute  uephritis  and  an  entire  hosl  of  nervous  phenomena. 

The  therapy  consists  in  immediate  gastric  lavage  and  in  the  administration 

of  magnesium  sulphate  and  -odium  sulphate. 

The  prognosis  i-  very  grave ! 

I  have  included  this  form  of  poisoning  because  the  barium  -alts  are  reme- 
dies which  enormously  increase  blood  pressure,  and  therefore  barium  chlorid 
has  been  employed  in  place  of  calomel  in  disturbances  "I'  cardiac  compensation. 

The  severe  symptoms  of  this  poisoning,  I  might  say  the  absolute  impossi- 
bility of  relying  upon  the  action  of  these  -alt-,  forces  me  to  advise  against 
their  use,  even  should  these  -alt-,  a-  hear!  tonic-,  find  eulogists  in  the  future. 

We  now  proceed  to  another  group  of  poisonous  agents,  the  metalloids. 
The  lir.-t  to  be  considered  are  chlorin.  bromin  and  iodin.  with  their  combina- 
tion.-.     Only   two  of   the  OHLORIN   COMBINATIONS  are  of   practical    importance. 

namely,  chloral   hydrate  and  chloroform.     The  iir-t    is  used  a-  a   hypnotic; 
but  it  is  not  a  harmless  remedy,  since  upon  long-continued  use  it  may  give  rise 


584  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

to  psychical  depression,  and  according  to  all  appearances,  to  progressive  paral- 
ysis ;  and,  moreover,  in  persons  affected  with  disease  of  the  heart,  even  in  rela- 
tively small  doses  (2  to  3  grams)  it  may  cause  death.  We  should,  therefore, 
be  most  cautious  in  the  use  of  this  remedy,  sometimes  so  necessary,  for  exam- 
ple, in  the  treatment  of  certain  forms  of  delirium  tremens!  In  cardiac  dis- 
eases, particularly,  the  use  of  chloral  hydrate  is  contraindicated ! 

The  second  remedy  to  be  discussed  is  chloroform.  Every  one  knows  the 
blessing  of  its  effect,  and  it  is  to  be  hoped  that  the  physician  may  be  spared 
any  exhibition  of  its  deleterious  action  during  his  professional  career! 
Chloroform  is  a  potent  cardiac  poison,  and  the  sudden  deaths  in  narcosis  which 
occur  from  time  to  time  may  be  referred  to  this  circumstance.  There  can  be 
no  doubt  that  chloroform  narcosis  may  produce  permanent  damage  to  the 
organism,  such  as  fatty  degeneration  of  the  heart  and  of  the  liver,  and  for 
this  reason  our  motto  must  be :  Be  cautious  in  the  use  of  chloroform,  whether 
employed  as  an  anesthetic  or  internally !  I  shall  not  detail  the  symptoms. 
These  are  generally  known.  Fatalities  can  never  be  entirely  prevented  in 
chloroform  anesthesia,  but  careful,  minute  investigation  of  the  heart  of  the 
patient  who  is  to  be  anesthetized  with  chloroform  will  certainly  limit  them  to  a 
great  extent.  We  must  hope  that  the  time  is  not  far  distant  when  less  dan- 
gerous anesthetics  will  be  substituted  for  chloroform  narcosis.  A  beginning 
has  already  been  made  in  this  direction  by  Schleicht  infiltration  anesthesia. 

In  the  second  halogen,  the  bromin  salts  shall  be  briefly  mentioned ;  these 
are  extensively  used  in  medicine,  and  thus  cause  the  development  of  that 
pathologic  picture  which  we  appropriately  designate  as  bromism.  Although 
we  cannot  avoid  using  the  salts  of  bromin  in  the  treatment  of  epilepsy,  and 
although  recent  observations  have  shown  that  the  administration  of  the  salts 
of  bromin  in  food  free  from  chlorin  or,  at  least,  almost  free  from  it,  is  rela- 
tively well  borne,  on  the  other  hand  we  cannot  deny  that,  particularly  in  pre- 
disposed individuals,  even  the  therapeutic  use  of  bromin  may  cause  serious 
symptoms  of  bromism.  It  is  possible  that  the  administration  of  bromin  in 
sesame  oil  may  mitigate  these  symptoms,  but  it  cannot  be  expected  to  prevent 
their  appearance  entirely.  The  symptoms  are  anorexia,  metallic  taste,  dys- 
pepsia, decided  emaciation,  dermatoses  of  many  varieties;  also  a  series  of 
psychical  and  nervous  disturbances,  particularly  loss  of  memory,  and  these 
may  lead  to  the  development  of  the  severest  psychical  symptoms.  The  salts 
of  iodin  act  in  a  similar  manner,  except  that  here,  as  a  rule,  emaciation, 
I  might  say  all  the  somatic  symptoms,  take  precedence  of  the  psychical 
element. 

We  now  turn  to  another  of  this  group  of  poisons,  to  phosphorus,  which, 
at  least  in  Austria,  assumes  uncommonly  great  importance,  for,  in  certain 
cities — especially  in  Prague,  next  in  Vienna,  less  frequently  in  the  country — 
the  number  of  poisonings  by  this  agent,  which,  in  the  course  of  the  year,  come 
under  the  observation  of  the  physician,  is  an  unusually  large  one.  Almost 
exclusively  the  cases  are  suicidal,  although  the  poison  is  often  taken  to  bring 
about  abortion.  But  the  clinical  picture  of  poisoning  by  phosphorus  has 
additional  interest  from  the  fact  that  a  number  of  other  toxicoses,  even  a  num- 
ber of  diseases  for  the  most  part  infectious,  present  or  may  present  a  picture 


METALLOIDS  585 

resembling  poisoning  from  phosphorus.  Mushroom  poisoning  (which  see) 
is  an  example  of  such  toxicosis,  and,  of  other  diseases,  acute  yellow  atrophy  of 
the  liver. 

What  symptoms  are  produced  by  poisoning  with  sticks  of  phosphorus? 
A  few  hours  after  the  ingestion  of  the  poison,  nausea  and  a  tendency  to  vomit, 
more  rarely  actual  vomiting,  appears;  the  patient  is  uncommonly  restless; 
jaundice,  which  may  occur  upon  the  first  or  the  second  day  after  the  poison- 
ing, indicates  the  severity  of  the  intoxication.  Usually  we  see  decided  enlarge- 
ment of  the  liver,  which  may  even  appear  a  few  hours  after  the  poisoning. 
The  evidences  of  the  hemorrhagic  diathesis  and  fever  are  added  to  this,  and 
in  a  few  days  the  patient  succumbs  from  his  suffering.  In  the  majority  of 
cases  of  poisoning  with  phosphorus  it  is  fatty  degeneration  of  the  heart  which 
causes  death.  The  later  jaundice  appears,  the  more  favorable  the  prognosis; 
a  good  appetite,  or  even  a  sensation  of  hunger,  is  a  favorable  sign  in  the  course 
of  phosphorus  toxicosis.  In  the  severe  cases  the  urine  contains:  Biliary  col- 
oring matter  and  albumin;  not  rarely,  if  large  amounts  of  grape  sugar  be 
administered  to  the  patient,  sugar  is  also  present  :  that  i-,  an  alimentary  glyco- 
suria arises,  a  symptom  which,  according  to  my  experience,  is  intimately  con- 
nected with  the  changes  produced  in  the  liver  by  this  toxicosis. 

What  is  the  besl  treatment  for  phosphorus  poisoning?  I  know  of  but 
one  reliable  remedy:  Thorough  gastric  lavage  performed  at  once.  The  earlier 
and  the  more  actively  this  is  carried  out  the  more  certain  the  result:  never- 
theless, even  cases  in  which  enormous  amounts,  up  to  0.7  gram,  of  phos- 
phorus have  been  takes  may  terminate  in  recovery,  as  is  shown  by  a  case  of 
my  own.  I  also  use  sulphate  of  copper,  solutions  of  old  oil  of  turpentine, 
hydrogen  peroxid,  and  potassium  permanganate,  and  I  musl  admit  that  these 
agents  produce  certain  favorable  effects,  but.  as  a  sovereign  remedy  in  the 
treatment  of  poisoning  from  phosphorus,  they  do  not  equal  gastric  lavage,  in 
which  -'!<)  to  to  liter-  of  water  may  he  used,  and  this  should  I»'  continued  until 
the  fluid  no  Longer  has  the  faintesl  smell  of  phosphorus.  The  chemical  proof  of 
phosphorus  in  the  vomited  material  or  in  the  feces  i-  very  easy:  Two  piece-  of 

filter  papei  are  moistened,  one  with  a  solution  of  nitrate  of  silver,  the  other 

with  a  solution  of  lead  acetate;  both  are  then  dipped  in  the  material  to  he 
tested.  If  the  Bilver  nitrate  portion,  owing  to  the  reduction  of  sali  of  Bilver, 
show-  a  black  discoloration,  this  proves  that  phosphorus  is  present.  When 
the  lead  portion  becomes  black  the  result  is  uncertain,  for  then  the  reaction 
may  have  been  brought  about  by  hydrogen  sulphid.  and  this  i-  particularly 
prone  to  occur  if  the  feces  are  examined.  If  the  te-t  i-  positive,  i.e..  if  the 
lead    portion    is    not    blackened,  certain    proof   is    furnished    that    poisoning   by 

phosphorus  is  present.  I  musl  remark  here  that  a  positive  resull  in  the  te-t 
of  the  feces  always  renders  the  prognosis  unfavorable,  for  this  reaction  shows 
that  the  phosphorus  ha-  passed  through  the  entire  intestine,  and  bo  ha-  in  all 
probability  been  taken  up  into  the  organism.  In  Buch  cases  we  mu-t  endeavor 
to  eliminate  the  pho-phuru-  from  the  intestine  a-  rapid!}  a-  possible,  the  besl 
mean-  being  by  the  administration  of  an  infusion  of  aenna.  Much  thai  is 
interesting  regarding  phosphorus  poisoning  might  still  be  mentioned,  Buch  as 
the   relation-    between    poisoning  by    phosphorus   and   acute  yellow   atrophy  of 


586  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

the  liver  and  certain  forms  of  mushroom  poisoning,  but,  unfortunately,  these 
are  bej'ond  the  limits  of  this  article. 

Some  reference  must  be  made  to  chronic  phosphorus  poisoning  which  is 
the  terror  of  the  workman  in  the  manufacture  of  phosphorus  matches;  and 
presents  itself  in  the  form  of  a  phosphorus  necrosis  of  the  lower  jaw.  In 
Austria,  on  account  of  the  excellent  hygienic  measures  enforced  by  the  super- 
vision of  the  Government,  this  form  of  the  disease  has  become  a  rarity. 

We  now  turn  to  another  agent,  sulphur  and  its  combinations,  of  which 
poisoning  by  sulphureted  hydrogen  and  carbon  bisulphid  are  the  most  im- 
portant. 

Poisoning  with  sulphureted  hydrogen  is  rare,  but  occurs  most  frequently 
in  chemical  laboratories  and  among  workmen  in  latrines.  If  the  gas  is  pres- 
ent in  great  amounts,  and  the  air  is,  therefore,  relatively  deficient  in  oxygen, 
the  affected  individual  soon  shows  the  severest  symptoms,  and  rapidly  perishes. 
In  less  severe  cases  there  is  debility,  weakness  and  vomiting  occur,  followed 
by  fibrillary  muscular  contractions,  etc.  Generally  this  form  of  poisoning  is 
of  slight  importance.  On  the  other  hand,  poisoning  by  carbon  bisulphid 
occurs  more  frequently,  and  leads  to  very  interesting  changes  in  the  retina 
which  until  recently  have  been  but  little  studied. 

We  now  turn  to  a  very  important  toxicosis,  that  of  arsenic  and  its  com- 
binations. 

All  soluble  combinations  of  arsenic  are  poisonous!  The  symptoms  vary 
according  to  the  amount  of  the  poison  ingested,  the  ready  solubility  or  insol- 
ubility of  the  substance,  and  the  state  of  the  stomach ;  if  taken  on  a  full 
stomach  the  phenomena  appear  less  rapidly  than  on  an  empty  stomach. 

In  the  severest  form,  asphyxia  arsenicalis,  symptoms  arise  which  very 
closely  resemble  the  clinical  picture  -of  cholera  Asiatica  and  in  a  few  hours  may 
cause  death.  I  refer  to  such  symptoms  as  vomiting,  diarrhea,  rice-water-like 
stools,  and  cramps  in  the  calves  of  the  legs ;  in  less  severe  cases  the  same  symp- 
tom-complex is  produced — although  less  rapidly — and  the  symptoms  of  toxic 
enteritis   (purulent  stools,  tenesmus,  etc.)   are  more  prominent. 

A  positive  diagnosis  can  only  be  made  when  arsenic  is  found  in  the  vom- 
ited material  and  in  the  excretions,  for  which  purpose  it  is  necessary  to  de- 
termine the  presence  of  arsenic  by  positive  methods,  and  to  isolate  it:  If 
arsenious  acid  has  been  employed,  an  accurate  microscopic  investigation  will 
occasionally  demonstrate  that  this  substance  is  present:  The  white  particles 
are  extracted  with  a  forceps  from  the  vomited  material,  rinsed  with  water, 
and  dissolved  in  hot  water;  upon  cooling,  the  characteristic  small  octahedra 
of  arsenious  acid  are  found  as  crystals. 

What  must  be  done  in  the  treatment  of  tin's  condition?  The  answer  is 
this:  Immediate  and  thorough  lavage  of  the  stomach,  administration  of  cal- 
cined magnesium  in  water,  also  washing  out  the  stomach  with  this  preparation 
and  the  administration  of  Bunsen's  remedy,  namely,  hydrated  ox  id  of  iron; 
if  at  hand,  lime  water  may  be  employed;  by  frequent  and  copious  enemata,  the 
intestine  must  be  emptied,  and  the  poison  thus  expelled  from  the  bowel. 

Chronic  arsenic  poisoning  is  very  interesting  on  account  of  the  extreme 
cachexia,  the  severe  nervous  disturbances  such  as  polyneuritis,  etc.,  and  the 


METALLIC  SALTS  5S7 

verv  peculiar  cutaneous  melanoses  to  which  these  conditions  lead  and  which 
have  lately  been  much  studied.  The  therapy  must  be  strictly  adapted  to  each 
individual  case.     It  is  impossible  to  enter  into  its  details. 

Poisoning  by  arseniureted  hydrogen  must  be  briefly  referred  to.  This 
is,  of  late,  not  rare  in  chemical  laboratories  and  in  chemical  factories.  The 
cases  run  a  severe  course,  but  frequently  terminate  favorably.  Jaundice, 
hematuria,  various  spasms  form  the  most  important  symptoms,  i.  e.,  the  course 
is  entirely  different  from  that  of  poisoning  with  the  salts  of  arsenic !  The 
therapy  consists  only  in  strict  prophylaxis:  Avoidance  of  all  chemical  proc- 
esses  in  open  spaces  in  which  arseniureted  hydrogen  can  possibly  develop. 

We  now  turn  to  another  form  of  toxicoses:  Poisoning  with  metallic  salts, 
metallism.  From  the  enormous  number  of  metallic  salts  which  could  be  men- 
tioned here,  I  shall  only  emphasize  poisoning  with  lead  and  mercury  as  of 
practical  importance. 

Acute  poisoning  with  salts  of  lead  is.  upon  the  whole,  of  comparatively 
slight  interest,  but  much  more  important  are  the  chronic  lead  TOXICOSES. 

Regarding  the  former,  a  metallic  taste,  a  sensation  of  dryness  and  burning 
in  the  mouth  and  throat,  and  severe  colic-like  pains  are  the  most  important 
symptoms;  later  obstinate  vomiting  occur-,  and  the  vomited  material  often 
shows  a  hemorrhagic  discoloration.  A  diagnosis  of  acute  poisoning  with  the 
salt  of  lead  cannot  be  certainly  made  from  these  symptoms,  but  the  presence 
of  lead  salts  in  the  vomited  material,  the  history,  the  corpus  delicti,  i.e.,  the 
investigation  of  the  salt  which  may  be  at  hand,  the  fluid,  etc.,  render  the 
diagnosis  of  acute  lead  poisoning  possible.  The  immediate  administration  of 
milk,  of  solutions  of  albumin,  of  sodium  sulphate  and  magnesium  sulphate 
which  reduce  lead  combinations  to  an  insoluble  lead  sulphate,  is  recommended. 

it  is  most  important  for  the  physician  to  recognize  chronic  lead  poisoning, 
partly  because  of  the  frequency  of  its  occurrence,  and  partly  because  it  mani- 
fests itself  in  such  various  ways. 

Lead  poisoning  from  occupation,  as  in  type-setters,  painters,  gas-fitters, 
etc.,  i-  usually  preceded  by  symptoms  of  lead  colic:  The  patients  are  seized 
with  paroxysms  of  severe  cutting  pains  in  the  abdomen,  an  attack  in  its  great- 
est intensity  rarely  Lasting  longer  than  a  quarter  of  an  hour,  and  after  a 
shorter  or  Longer  interval  the  Bevere  paroxysms  of  pain  Bel  in  anew.  The 
abdomen  is  retracted,  there  is  constipation,  the  pulse  is  slow.  The  physician 
must  act  at  once.     A  Lukewarm  bath  will  often  relieve  the  paroxysms  of  pain 

in   the  briefest    time;   but    the  patient    should    not    be  allowed    to  Buffer,  and    if 

this  is  not  effective,  morphin  Bubcutaneously  should  lie  employed;  0.005  gram, 
certainly  0.01  gram,  hypodermically  employed,  will  in  a  -bort  lime  relieve 
the  attack.  Bui  the  serious  Bymptoms  of  chronic  lead  toxicosis  can  only  be 
averted  if  the  patient,  in  the  future,  carefully  avoid-  contact  with  combina- 
tions of  lead    or   working  with   -alts  of   lead.      If  he    fail    to  do   this,   the   lir-t 

attack  i-  succeeded  by  a  Becond,  a  third,  etc.,  and  the  serious  tragedy  of  chronic 
lead  poisoning  begins. 

Sometimes,  besides  the  pale  appearance,  the  excruciating  pains  in  the 
joints  (arthralgia),  paresthesia,  various  disturbances  of  sensation  torment  the 
patient;  in  many  cases  he  i-  spared  these  symptoms,  but   weakness  in  the 


588  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

hands  occurs,  the  hands  are  moved  with  difficulty,  or,  finally,  can  no  longer 
be  extended:  The  unfortunate  condition  of  bilateral  radial  paralysis  develops 
(wrist-drop).  Sometimes  the  havoc  ceases  there;  no  other  symptoms  appear; 
but  radial  paralysis  renders  the  patient  incapable  of  working  for  a  long  time, 
and  frequently  for  life. 

The  condition  becomes  more  serious  if  there  is  evidence  of  grave  cere- 
bral disease;  symptoms  of  encephalitis,  epilepsy,  mania,  briefly,  mental  dis- 
turbances of  all  kinds,  indicate  how  seriously  this  poison  influences  the  brain. 
Because  of  these  disturbances  the  prognosis  is  very  serious;  and  unless  dis- 
ease of  another  organ,  consequent  upon  this  toxicosis,  particularly  the  lead 
kidney,  terminates  the  life  of  the  unfortunate  patient,  the  insane  asylum  is 
likely  to  be  his  final  resort. 

The  terrible  nature  of  lead  poison  is  thus  apparent,  and  yet  I  have  men- 
tioned but  a  few  signs  of  this  toxicosis.  It  must  be  added  that  metabolism  is 
most  unfavorably  influenced  by  lead,  in  that  it  leads  to  an  increased  forma- 
tion and  excretion  of  uric  acid,  and  thus  produces  symptoms  which  are  also 
observed  in  arthritis  urica  (gouf). 

What  remedial  agents  does  therapy  furnish  with  which  to  combat  these 
conditions,  and  what  treatment  must  be  adopted  if  the  phenomena  described 
have  already  appeared  ?  Eegarding  the  first  point,  only  a  careful  prophylaxis 
is  in  order.  Workmen  in  lead  who  have  once  recovered  from  lead  colic  must 
always  change  their  occupation;  the  dangers  to  which  they  are  subjected 
must  be  fully  explained  to  them,  and  they  should  be  induced  to  seek  other 
means  of  support  which  do  not  bring  them  into  contact  with  combinations 
of  lead.  If,  however,  the  unfortunate  symptoms  are  present,  i.  e.,  radial 
paralysis,  we  may  attempt  to  improve  the  condition  by  the  employment  of 
electricity,  massage,  particularly  vibratory  massage,  also  by  the  administra- 
tion of  preparations  of  iodin,  such  as  sodium  iodid,  iodipin  (10  per  cent, 
solution),  and  furthermore,  by  the  use  of  baths.  In  the  main  we  must  admit 
that  in  radial  paralysis,  encephalitis,  epilepsy,  etc.,  due  to  lead  toxicosis,  we  are 
almost  powerless. 

A  word  regarding  the  diagnosis.  In  the  characteristic  "lead  line,"  the 
peculiar  bluish  discloration  of  the  mucous  membrane  of  the  mouth  in  those 
areas  in  which  the  teeth  are  implanted  in  the  jaws,  we  have  a  cardinal  symp- 
tom of  lead  toxicosis.  It  is  true  this  symptom  may  be  explained  in  many 
ways,  since  various  factors,  for  example,  tooth  powder  which  contains  wood 
charcoal,  chronic  mercury  poisoning  in  workmen  in  iron  and  iron  salts,  may 
produce  a  symptom  which  sometimes  very  closely  resembles  this.  Hence  a 
diagnosis  should  never  be  made  from  the  lead  line  alone.  If,  however,  other 
symptoms,  particularly  colic,  favor  the  view  that  we  are  dealing  with  lead 
toxicosis,  the  presence  of  the  lead  line  may  be  considered  to  confirm  this  diag- 
nosis, the  more  so  as  the  chemical  proof  of  lead  in  the  secretions,  for  example, 
in  the  urine,  is  frequently  negative,  particularly  in  the  late  stages  of  the 
disease. 

In  practical  importance  mercurial  poisoning  may  be  placed  side  by  side 
with  saturnine  poisoning.  Since  the  soluble  combinations  of  mercury  have 
been  utilized  as  antiseptics  in  therapy,  the  number  of  cases  of  acute  as  well  as 


METALLIC  SALTS  589 

chronic  poisoning  by  mercury  has  been  enormously  increased,  although  re- 
cently, since  the  recognition  of  the  danger  in  this  antisepsis,  the  number  has 
been  lessened  by  a  more  judicious  use  of  mercury. 

All  salts  of  MEBGUBY  arc  poisonous!  It  is  true  the  number  of  poisonings 
which  have  been  observed,  for  example,  with  mercuric  sulphate,  with  mer- 
curic iodid,  etc.,  are  exceedingly  small  in  comparison  with  the  number  of 
poisonings  with  corrosive  sublimate,  the  hydrargyrum  bichloratum  corrosivum 
(mercuric  chlorid).  These  should  not  be  confounded  with  mercurous  chlorid, 
calomel,  which,  in  much  smaller  doses,  also  has  a  toxic  effect.  I  saw  a  case  in 
which  six  grams  had  been  taken  with  suicidal  intent,  yet  it  was  followed  by 
recovery  in  a  few  days.  The  lethal  dose  of  chlorid  of  mercury  in  our  popula- 
tion is  about  0.2  gram  ;  I  say  in  our  population,  because  the  opium  smokers 
in  China  can  bear  enormous  doses  of  corrosive  sublimate. 

In  acute  toxicosis  with  mercury,  therefore,  we  shall  discuss  only  the  clin- 
ical symptoms  produced  by  corrosive  sublimate.  In  the  chronic  form  we  shall 
concern  ourselves  more  or  less  with  all  of  the  salts,  and  metallic  mercury, 
even  the  fumes  of  mercury,  will  be  taken  into  consideration. 

What  are  the  symptoms  of  poisoning  by  corrosive  sublimate  } 

If  the  poison — as  in  the  majority  of  eases — is  introduced  through  the 
moutb,  widely  distributed  eschars  at  once  appear  upon  those  areas  of  the 
mucous  membrane  which  have  come  in  contact  with  the  poison.  Violent  vom- 
iting appears;  the  vomitus  is  admixed  with  blood,  and  later  with  shreds  of 
mucous  membrane.  Colicky  pains  and  profuse  diarrhea  follow,  there  is  sup- 
pression of  urine  or  else  but  a  small  amount  of  hemorrhagic  urine  is  voided. 
Even  at  this  stage  a  fatal  termination  may  ensue;  the  subnormal  temperature 
and  the  small  pulse  with  low  tension  indicate  the  approaching  end.  usually, 
however,  the  sufferings  of  the  patient  are  decidedly  prolonged.  The  deeply 
penetrating  eschars  cause  agonizing  pain,  ulcerative  stomatitis,  parotitis. 
annoying  salivation  increase  the  distress.  Gastritis  and  ulcerative  enteritis 
with  all  of  their  consequences  Bupervene.  The  Bymptoms  on  the  pari  of  the 
kidney  become  more  intense.  The  scanty  urine  -how-  the  characteristics  of 
acute  nephritis.  After  days  of  misery  the  patient  succumbs  to  uremic 
toxicosis. 

In  all  cases  of  poisoning  with  corrosive  sublimate  the  prognosis  is  Berious. 
Even  apparently  mild  cases  may  develop  acute  nephritis  and  terminate  fatally. 

Pot  certainty  in  diagnosis  the  presence  of  mercury  musl  be  proven  in  the 
vomited  material,  in  the  urine,  and  perhaps  in  the  feces.  In  a  number  of 
cases  the  history  and  the  typical  Bymptoms  will  at  once  indicate  the  correct 
diagnosis. 

The  therapy  consists  in  immediate  and  thorough  lavage  of  the  Btomacb 
with  milk  and  solutions  of  albumin.  Table  -alt  increases  the  solubility  of 
corrosive  Bublimate  and  therefore  cannot  he  employed.     Stomatitis  i-  to  be 

treated  with  -olutions  of  potassium  chlorate,  the  anuria  with  lukewarm  hatb- 
and by  venesection.     The  severe  pain  Qecessitates  the  age  of  opiates, 

We  re .w  turn  to  chronic  mercurial  poisoning.  This  occurs  mosl  commonly 
among  workers  in  certain  industries, 

1  should  like  here  t<>  emphasize  the  fad  that   mercurial  treatmenl  care- 


590  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

fully  conducted  and  based  upon  a  correct  diagnosis  has  never  produced  in  any 
patient  the  symptoms  of  chronic  mercury  toxicosis ! 

The  symptoms  in  the  beginning  resemble  those  of  lead  poisoning:  pallor, 
dyspepsia,  the  appearance  of  a  black  line  upon  the  gums  (see  p.  588),  but  the 
typical  colic  of  lead  poisoning  is  absent.  The  patient  emaciates.  Diarrhea, 
stomatitis  and  salivation,  and  various  dermatoses,  such  as  erythema,  eczema, 
furunculosis,  and  ulcers  of  the  skin,  appear.  Nervous  symptoms,  such  as 
tremor  and  polyneuritis,  follow.  These  are  the  signs  of  increased  psychical 
irritability  (erethismus  mercurialis),  and  finally,  severe  psychical  depression 
(coma).  All  this  makes  the  life  of  the  patient  miserable,  and  may  shorten 
it.  But  a  greater  danger  consists  in  the  fact  that  the  kidney  may  be  attacked, 
and  after  years  of  invalidism  the  patients  often  succumb  to  the  symptoms  of 
contracted  kidney  or  of  chronic  nephritis,  and  even  without  nephritic  symp- 
toms some  patients  may  succumb  to  marasmus  praecox  relatively  early  in  life. 

The  prognosis  in  the  first  stages,  in  case  no  nephritic  symptoms  are  pres- 
ent, is  not  unfavorable;  in  the  later  stages,  particularly  if  psychical  disturb- 
ances have  appeared,  it  is  always  serious.  In  treatment,  preparations  of 
iodin  and  bromin  (sodium  iodid,  iodipin,  etc.)  are  most  efficacious.  Sulphur 
baths  are  also  used.  With  intact  kidneys,  pilocarpin,  in  the  form  of  subcu- 
taneous injections,  may  render  good  service. 

We  now  turn  to  another  chapter :  Poisoning  with  gases. 

For  the  physician  only  carbonic  oxid  poisoning  has  acquired  great  im- 
portance. This  toxicosis  offers  a  fruitful  field,  and  it  is  necessary  for  him 
to  be  acquainted  with  its  pathology  and  therapy. 

Illuminating  gas,  which  contains  from  7  per  cent,  to  10  per  cent,  of  car- 
bonic oxid  gas,  and  the  fumes  of  charcoal,  which  contain  about  0.2  per  cent, 
to  0.-4  per  cent.,  are  the  sources  of  this  poisoning,  the  former  by  the  presence 
of  the  gas  in  rooms  where  it  is  in  use,  the  latter  by  the  escape  of  charcoal  fumes. 
Danger  may  therefore  arise  from  defective  or  misused  gas  fixtures  and  from 
badly  constructed  stoves,  and  in  case  of  fire. 

Of  the  initial  symptoms  of  the  poisoning  little  is  known.  Vomiting  occurs 
frequently  in  this  stage,  and  often,  if  the  patient  be  unconscious,  the  entrance 
of  food  or  vomitus  into  the  trachea  may  cause  death  by  suffocation.  In  the 
stage  at  which  the  physician  usually  arrives,  the  patient  is  unconscious,  pro- 
foundly asphyxiated.  The  temperature  is  low,  cardiac  action  weak  and  irregu- 
lar, the  pulse  quickening,  and  in  a  few  hours  death  occurs.  Elevations  of 
temperature  up  to  102.2°  F.,  and  nervous  irritative  symptoms,  such  as  trismus, 
tonic  and  clonic  spasms,  are  not  rare.  Because  of  the  anesthesia  coincident  with 
coma,  patients  may  be  severely  burned  during  treatment.  The  sequels  which 
may  follow  this  toxicosis  are  particularly  serious.  These  are  chorea,  polio- 
myelitis, trophic  disturbances  of  all  kinds,  gangrene,  etc.  Metabolism  is  also 
seriously  deranged ;  alimentary  glycosuria  is  an  invariable  symptom  and  spon- 
taneous glycosuria  frequently  occurs. 

The  diagnosis  is  easy  on  account  of  the  characteristic  symptoms.  For  the 
detection  of  carbonic  oxid  in  the  blood  I  advise  the  examination  of  blood 
obtained  by  venesection.  A  portion  should  be  diluted  with  about  20  times 
as  much  water,  and  then  boiled  with  caustic  potash.    If  carbonic  oxid  be  pres- 


FAT   BODIES  591 

ent  the  solution  becomes  first  turbid,  then  of  a  light  red  color.  Normal  blood 
under  these  circumstances  always  assumes  a  dirty  brownish  hue.  The  pres- 
ence of  carbonic  oxid  hemoglobin  in  the  blood,  determined  by  the  spectroscope, 
may  also  facilitate  the  diagnosis. 

The  treatment  of  this  condition  may  be  considered  as  fairly  established. 
The  sovereign  remedy  is  profuse  venesection  with  a  subsequent  normal  saline 
infusion.  This  is  to  be  followed  by  a  lukewarm  bath  with  cold  affusions. 
I  have  rarely  found  it  necessary  to  proceed  to  the  latter  measures,  for  since 
I  have  treated  every  case  of  carbonic  oxid  toxicosis  by  venesection  and 
normal  salt  infusion — whether  by  accident  or  as  an  actual  result  of  therapy 
— in  my  hospital  service  I  have  lost  no  case  of  carbonic  oxid  toxicosis.  In  pri- 
vate practice,  however,  I  had  two  cases  of  carbonic  oxid  poison,  illuminating 
gas,  which  ran  their  course  with  very  peculiar  nervous  symptoms  and  after  a 
duration  of  several  days  terminated  fatally.  Chronic  carbonic  oxid  poisoning 
is  a  result  of  inhaling  for  a  long  time  an  atmosphere  which  contains  slight 
amounts  of  carbonic  oxid.  Dyspepsia,  anemia,  jaundice,  splenic  tumor,  and 
various  symptoms  of  a  nervous  nature  form  the  interesting  pathology  of  this 
toxicosis. 

We  now  proceed  to  the  discussion  of  poisoning  by  those  substances  which 
belong  to  the  fat  bodies — the  methane  derivatives. 

The  number  of  these  derivatives  is  legion.  Those  interesting  to  the  physi- 
cian are  few:  namely,  poisoning  with  ethyl  alcohol,  with  sulphonal,  trional  and 
tetronal. 

Ethyl  alcohol  is  one  of  the  most  violent  poisons.  We  may  say  that 
there  is  no  organ,  no  cell  of  the  human  organism,  which  is  not  subject  to 
deleterious  influence  from  alcohol. 

Even  a  single  acute  intoxication  with  alcohol,  a  debauch,  may  cause  incal- 
culable harm  and  lead  to  severe  damage  of  the  organism.  It  may  give  rise  t<> 
a  long-continued  gastric  catarrh,  to  symptoms  of  polyneuritis  and  of  renal 
irritation — although  thousands  and  thousands  of  cases  of  acute  alcohol 
intoxication  do  not  produce  such  Berious  consequences.  The  symptoms  of  alco- 
hol intoxication  are:  At  firsl  a  stage  of  exaltation,  with  a  series  of  nervous 
symptoms,  among  which  spasms,  which  are  observed  particularly  in  infancy. 
must  he  emphasized.  This  is  followed  by  deep  coma,  in  which  the  patient 
succumbs  to  tin-  toxicosis.  Tin-  greatest  enemy  of  such  patients  is  cold,  and  a 
low  externa]  temperature  not  infrequently  causes  death. 

The  treatment  of  acute  alcohol  intoxication  consists  in  the  immediate 
washing  out  of  the  Btomach  and  the  employment  of  lukewarm  hath-  with  cold 
affusions.    Cutaneous  irritants,  such  as  Binapisms,  and  even  tin'  subcutaneous 

OS€  ->f  a!  POpin,  may  he  indicated. 

A  much  more  serious  affection,  and  one  peculiar  to  alcoholics,  is  delirium 

tremens.  This  i<  an  acute  psychosis  which  in  persons  addicted  in  alcohol  fre- 
quently appears  a-  an  ominous  and  dangerous  complication  of  acute  diseases. 

In  the  treatment  of  delirium  trements  chloral  hydrate  and  opium  in  the 
form  of  ehemata  are  beneficial. 

'I'he  symptoms  of  chronic  alcoholism  are  of  grave  import.     Primarily,  it 

LB  the  kidney  which  i-  attacked,  and   with  the  result   particularly  of  contracted 


592  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

kidney.  The  abuse  of  alcohol  at  a  relatively  early  age  may  produce  arterio- 
sclerosis also.  Cutaneous  changes  of  all  kinds — acne,  dilatation  of  the  veins — 
may  be  due  to  chronic  alcoholism.  The  influence  upon  the  liver  is  particu- 
larly prominent  and  typical;  alcoholic  cirrhosis  with  ascites,  caput  Medusas, 
the  small,  tough  degenerated  liver,  form  a  clinical  picture  peculiar  to  this 
disease.  An  entire  array  of  nervous  diseases  as  well,  such  as  polyneuritis,  etc., 
and  apoplexy  due  to  arteriosclerosis,  threaten  the  alcoholic,  who  frequently 
indeed  betrays  himself  as  such  by  the  tremor  of  the  hands. 

The  proper  therapy  of  chronic  alcoholism  requires  primarily  the  avoidance 
of  alcohol  in  any  form.  In  such  cases,  however,  this  abstinence  usually  comes 
too  late,  for  alcohol  has  already  produced  irreparable  organic  changes.  For 
this  reason  all  our  efforts  must  be  directed  toward  lessening  the  abuse  of 
alcohol. 

The  modern  movement  against  the  use  of  alcohol  is  calculated  to  produce 
a  change  in  this  direction.  It  will  be  long  in  taking  deep  root,  but  its  prin- 
ciple is  correct.  Only  by  an  example  of  total  abstinence  may  we  hope  to  bring 
about  results.  In  writings  and  popular  lectures,  etc.,  this  standpoint  should 
be  defended,  and  finally  it  will  enable  us  to  combat  the  dire  consequences  of 
chronic  alcoholism. 

A  word  regarding  sulphonal,  trional  and  tetronal.  All  of  these 
remedies  are  useful  hypnotics,  but  they  are  also  poisons,  and  the  prolonged, 
continued  use  of  them  will  lead  to  hematoporphyrinuria,  a  very  serious  dis- 
turbance of  metabolism.  For  this  reason  the  greatest  care  is  necessary  in  their 
use,  and  the  continued  employment  of  them  should  be  prohibited. 

We  shall  now  devote  our  attention  to  cases  of  poisoning  produced  by  agents 
of  the  aromatic  group. 

The  fact  that  our  modern  antipyretics,  also  our  modern  antineural gics, 
belong  to  this  category  gives  them  special  importance. 

In  this  brief  article,  I  can  emphasize  few  symptoms,  but  must  confine 
myself  to  the  discussion  of  some  general  phenomena  of  this  poisoning. 

Above  all,  I  must  reiterate  the  fact  that  all  of  these  remedies  are  blood- 
poisons;  all  have  the  property  of  forming  methemoglobin  in  the  blood,  to 
which  we  may  probably  attribute  the  cyanosis  which  intoxication  with  these 
remedies  produces.  Furthermore,  the  majority  of  these  agents  are  combined 
with  sulphuric  acid  or  glycuronic  acid  in  the  organism,  and  are  excreted  from 
the  organism  as  combinations. 

The  symptoms  of  poisoning  by  nitro-benzol  (mirbane  oil,  artificial  bitter 
oil  of  almonds)  and  anilin  are  of  unusual  interest.  There  is  extreme  cyano- 
sis." Loss  of  consciousness  recurs  repeatedly  in  paroxysms — a  symptom  due  to 
the  changes  in  the  blood  produced  by  nitro-benzol  toxicosis  and  peculiar  to 
such  poisoning.  Although  these  toxicoses  show  exceeedingly  threatening 
symptoms — for  example,  pulmonary  edema — they  may,  nevertheless,  run  a 
favorable  course.  Nitro-benzol  poisoning  and  amido-benzol  poisoning  have 
lately  been  observed  frequently.  They  are  incident  to  certain  occupations, 
and  it  is  not  too  much  to  expect  that  since  the  danger  which  these  industries 
entail  has  been  recognized  proper  prophylaxis  will  in  future  make  such  cases 
of  poisoning  much  more  rare. 


AROMATIC  GROUP  593 

Among  the  bodies  of  this  group  greatest  interest  is  attached  to  phenol 
(hydroxybonzol,  carbolic  acid),  first,  because,  on  account  of  the  extensive  medi- 
cinal use  of  the  drug,  these  cases  of  poisoning  have  become  uncommonly  fre- 
quent, and  secondly,  because  the  course  of  this  poisoning  is  similar  in  type  to 
that  of  poisoning  by  the  hydroxylens  of  benzol. 

Phenol  in  concentrated  solution  causes  the  formation  of  eschars  upon  the 
skin  and  mucous  membrane;  even  local  necrose-  may  be  produced  or  stub- 
born acute  eczemas  which  may  be  distributed  over  the  entire  body.  In  spite 
of  this,  however,  the  dangers  would  be  slight  if  these  were  the  only  effects  of 
the  poison.  But,  introduced  into  the  organism  in  somewhat  larger  quantities, 
it  gives  rise  to  headache  vertigo,  spasms,  mydriasis,  tinnitus  aurium,  severe 
cyanosis  and  cardiac  collapse,  to  which  the  patient  may  succumb  in  a  short 
time.  Even  a  2  to  3  per  cent,  solution  injected  in  large  quantity  into  the 
pleural  cavity,  into  the  rectum,  etc.,  may  produce  this  effect. 

The  diagnosis  of  pheno-toxicosis  is  easy.  The  characteristic  odor  of  the 
breath,  the  very  dark,  discolored  urine,  deficient  in  Bulpho-sulphnric  acid, 
will  at  once  identify  the  case. 

In  regard  to  treatment,  if  the  poison  has  been  taken  through  the  mouth, 
the  stomach  should  be  washed  at  once.  This  is  best  done  with  water  and  wine 
vinegar  in  equal  amounts.  The  comatose  stage  should  be  treated  with  luke- 
warm hath-  and  cold  affusions.  Sugar  of  lime  and  sodium  sulphite  should  be 
employed  as  antidotes. 

The  best  practice  is  to  be  cautious  in  the  use  of  carbolic  acid  and  its 
preparation-  for  medical  purposes,  and  the  -ale  of  unauthorized  preparations 
Bhould  be  forbidden.  Even  dilute  solutions  should  never  be  used  for  washing 
out  the  cavities  of  the  body. 

Chronic  carbolic  toxicosis  is  an  evil  to  which  many  physicians  were  par- 
ticularly exposed  al  the  time  when  operations  were  carried  on  under  the  car- 
bolic Bpray,  a  method  which  has  now  been  abandoned.  Dermatoses  of  all 
varieties,  loss  of  memory,  renal  affections — briefly,  a  marasmus  praecox — are 
the  distressing  symptoms  of  this  toxicosis,  which  bas  now  almost  disappeared. 
The  prognosis  is  always  Berious.  A  number  of  physicians  have  succumbed 
to  this  poisoning,  but  it  is  now  pare. 

Analogous  affections  are  produced  by  other  derivatives  of  the  phenol  group, 
particularly  by  the  dioxybenzoles.  Picric  mill  (trinitrophenol)  causes,  as  an 
important  symptom,  a  yellow  discoloration  of  the  skin  which  is  not  due  to 
biliary  coloring  matter. 

Particular  Btress  musi  he  laid  upon  poisoning  with  rut:  salicylic  lcid, 
as  this  ha-  a  highly  corrosive  effect  upon  the  mucous  membranes,  and  thus 
gives  rise  to  Berious  gastroenteritis.  I  emphasize  this  because,  apparently 
through  ignorance  of  these  fact-,  free  salicylic  acid  is  repeatedly  advised 
medicinally,  and  I  desire  to  caution  physicians  againsl  its  ose!  The  salicylates 
are  also  poisons,  although  local  irritative  effects  are  not  peculiar  to  them: 
taken  in  very  large  doses,  or  by  individual-  who  are  very  susceptible  to  the 
action  of  salicylic  acid,  they  produce  toxic  phenomena  consisting  of  transitory 
amaurosis,  difficulty  in  hearing,  hematuria  and  hemoglobinuria.  In  contrasl 
with  free  Balicylic  acid,  however,  their  effed  is  relatively  -light. 
89 


594  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

Before  leaving  this  group  of  poisons,  I  must  refer  to  another  remedy  which, 
on  account  of  its  extensive  use  in  therapy,  often  gives  rise  to  toxicosis.  This 
drug  is  antipyrin.  Antipyrin,  at  one  time  the  favorite  and  most  extensively 
employed  antipyretic  and  antineuralgic,  is  also  a  poison  which  may  cause  severe 
symptoms  of  intoxication;  in  particular,  dermatoses  of  all  kinds,  the  hemor- 
rhagic diathesis,  and  many  cases  of  so-called  hemorrhagic  scarlatina  which 
are  not  due  to  the  intensity  of  the  disease,  but  to  the  intensity  of  the  therapy 
employed.  There  can  be  no  doubt  that  antipyrin,  besides  producing  exan- 
thematous  eruptions,  also  produces  enanthemas  of  the  most  varied  kinds.  In 
persons  who  show  an  idiosyncrasy  to  antipyrin — and  such  individuals  are  not 
rare — even  small  doses  may  produce  a  variety  of  eruptions.  It  is  true  that 
no  serious  phenomena  have  as  yet  been  noted  among  the  symptoms  of  antipyrin 
toxicosis ;  nevertheless,  the  therapeutic  employment  of  this  remedy  necessitates 
care,  all  the  more  so  as  its  continued  use  may  give  rise  to  the  symptoms  of 
chronic  antipyrin  toxicosis.  This  is  as  yet  but  little  known,  and  has  been  but 
little  studied,  the  condition  running  its  course  with  dyspepsia  and  gastric  and 
intestinal  catarrh. 

The  group  of  camphors  and  terpins,  ethereal  oils,  balsams  and  resins,  we 
shall  mention  but  briefly.  In  the  main  but  slight  importance  is  to  be  attached 
to  them.  Only  Japanese  camphor,  commonly  called  simply  camphor,  and 
employed  internally  as  the  oil  of  camphor,  is  of  importance  to  the  physician. 
There  is  no  doubt  that  the  introduction  of  large  quantities  of  camphor  into 
the  organism  causes  extreme  cerebral  irritation,  delirium,  spasms  and  convul- 
sions, even  albuminuria  and  severe  renal  irritation,  and  for  this  reason  it  is 
not  to  be  indiscriminately  used.  But  also  by  the  subcutaneous  employment 
of  the  oil  of  camphor — at  least  in  certain  affections,  such  as  enteric  fever — 
local  abscesses  may  be  produced,  even  with  the  most  cautious  asepsis.  I  do 
not  deny  the  favorable  effect  of  camphorated  oil  in  cardiac  collapse,  but  the 
experience  of  recent  years  shows  that  particular  care  is  necessary  in  the  em- 
ployment of  even  this  oil ! 

Some  remedies  which  are  in  common  use,  such  as  balsam  of  copaiba  and 
gamboge,  belong  to  this  group,  and  if  indiscreetly  employed  may  give  rise  to 
toxic  symptoms.  Toxic  nephritis  and  toxic  enteritis  may  be  produced  by 
these  agents,  and  for  this  reason  they  are  by  no  means  to  be  looked  upon  as 
indifferent  substances.  They  are  enumerated  here  only  that  I  may  recom- 
mend care  in  their  medicinal  employment. 

The  next  group  of  agents  with  which  we  shall  concern  ourselves  is  that 
of  the  alkaloids.  After  prussic  acid,  this  group  contains  the  most  violent  poi- 
sons for  the  human  organism,  poisons  which,  even  in  minimal  doses,  may  occa- 
sion the  severest  symptoms.  Chemically,  the  alkaloids  are  basic  bodies  which 
contain  a  pyridin  nucleus,  and  combine  with  acids.  Their  action  is  inde- 
pendent of  the  nature  of  the  acid,  but  depends  upon  the  nature  of  the  free 
base,  and,  therefore,  upon  the  nature  of  the  alkaloid.  All  these  agents  are 
characterized  by  the  fact  that  they  have  only  slight  local  action;  they  there- 
fore rarely  give  rise  to  gastritis  and  enteritis,  but  they  act  intensely,  even  in 
small  doses,  upon  the  heart  and  the  brain,  paralyzing  the  respiratory  center, 
and  in  this  way  rapidly  cause  death. 


ALKALOIDS  595 

A  number  of  these  alkaloids,  such  as  caff  ein,  thein,  and  nicotin,  are  con- 
tained in  substances  which  are  in  general  use,  such  as  tea  leaves  after  steeping, 
coffee  grounds,  and  tobacco;  therefore,  chronic  poisoning  by  these  alkaloids 
is  commonly  observed.  The  scope  of  this  article  doe-  qoI  permit  me  to  enu- 
merate all  of  the  alkaloids  familiar  to  us.  to  which  addition-  are  made  from 
year  to  year  by  the  discovery  of  new  alkaloids  in  the  vegetable  kingdom.  I 
shall  cite  the  effects  of  only  those  alkaloids  which  are  of  medical  importance, 
such  as  nicotin,  morphin,  atropin,  and  cocain.  The  symptoms  of  all  poison- 
ings due  to  alkaloids  is  quite  similar,  and  the  therapy  in  the  majority  of  cases 
is  in  the  main  analogous. 

Nicotin  ls  the  active  alkaloid  of  tobacco  leaves  (nicotians  tabaeum)  and 
the  differenl  products  manufactured  from  them.  Poisoning  with  this  exceed- 
ingly virulent  free  base  rarely  occur-,  and,  therefore,  is  of  no  practical  impor- 
tance. Mo-t  significant  are  those  forms  of  poisoning  by  tobacco  in  which. 
besides  nicotin,  other  deleterious  agents,  such  as  the  pyridin  bases,  carbonic 
oxid  and  prussic  acid.  etc..  collectively  give  rise  to  the  condition-  known  as 
acute  and  chronic  nicotinism. 

We  shall  lir.-t  describe  acute  nicotinism. 

I  may  be  brief,  for  every  one  who  has  smoked  knows  the  disagreeable  conse- 
quences of  the  first  attempt,  and  has  retained  the  effects  in  memory.  Headache, 
nausea,  vomiting,  diarrhea,  greal  debility  and  weakness  are  the  symptoms 
with  which  the  unaccustomed  organism  responds  to  the  poisonous  proper- 
ties of  tobacco.  Baths  with  cold  affusions  and  the  administration  of  alcohol 
will  rapidly  relieve  the  symptoms.  Tannin  and  dilute  lugol  solution  may  also 
be  employed  internally  in  severe  cases.  Usually,  however,  such  poisoning  runs 
a  favorable  course  in  a  few  hours,  and  only  a  headache,  which  sometimes  con- 
tinue- for  day-,  may  remain. 

More  important  than  acute  nicotin  poisoning  due  to  the  use  of  tobacco  is 
chronic  nicotin  poisoning  which  presents  itself  to  the  physician  in  a  different 
aspect.  Tachycardia,  arrhythmia,  and  cardiac  weakness  are  the  principal  and 
common  Bymptoma  in  this  toxicosis,  though  these  Bymptoms  are  susceptible 
of  different  explanation-.  Eow  far  Bevere  anatomical  changes  of  the  heart 
are  related  to  chronic  tobacco  to.\ico-i-  I  -ball  not  attempt  to  decide  ;  the  possi- 
bility of  such  an   occurrence  cannol    be  disputed.      Other  and    very   important 

symptoms  are  disturbance-  on  the  pari  of  the  eye-:  amblyopia,  amaun 
miosis  and  spasm  of  accommodation.     Weakness  of  memory  and  melancholic 
conditions  are  also  among  the  signs  of  chronic  aicotinism. 

The  treatment  consists  only  of  prophylaxis,  i.e..  the  moderate  use  of  nico- 
tin. Disturbances  of  sighl  are  to  he  relieved  by  keeping  the  patient  in  a 
darkened  room,  and  by  injection-  of  pilocarpi!)  and  strychnin. 

'I'he  next  alkaloid  to  he  considered  i-  morphin.     Opium,  the  dried  ju 
the  papaver  somniferum,  contain-  a  number  of  alkaloid-,  hut  the  symptom-  of 
poisoning  which  it  produces  are  all  closely  akin  to  those  due  to  morphin,  so 
that  we  may  consider  collectively  the  symptoms  which  these  agents  produce. 

Morphin  and  opium  are  two  of  the  mo-t   valuable  treasures  of  OUT  materia 

medica.     By  their  judicious  use,  the  physician  has  broughl  amelioration  to 
countless  numbers  of  sufferers,  hut  no  less  ha-  their  improper  use  caused  in- 


596  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

calculable  damage.  Opium  is  employed  extensively  in  the  Orient  and  slightly 
in  our  country  as  an  intoxicant  in  the  form  of  smoking.  Thus  used  it  causes 
severe  chronic  poisoning  to  which  I  shall  later  refer. 

We  shall  first  consider  the  consequences  of  the  introduction  into  the  body 
of  large  quantities  of  opium  or  morphin.  What  constitutes  a  large  quantity 
is  always  relative:  in  a  child  a  milligram  of  morphin  may  give  rise  to  the 
severest  symptoms,  while  the  morphinomaniac  addicted  to  morphin  may  take 
0.5  gram  and  more.  At  first  sopor  appears.  This  passes  into  deep  sleep. 
The  temperature  of  the  body  falls,  the  respirations  and  the  pulse  become  slow 
and  irregular,  the  pupils  are  narrowed,  the  scleras  injected,  and  in  a  few 
hours  the  adult  patient  succumbs  in  deepest  coma.  With  children,  as  shown 
by  the  observations  of  Eschle  and  myself,  spasms  are  prominent,  and  the  child 
succumbs  to  paralysis  of  the  respiratory  center. 

If  the  individual  withstands  the  shock  of  the  first  few  hours,  or  if,  by 
proper  treatment,  the  dangerous  stage  has  been  fortunately  passed  after  days 
of  coma,  consciousness  may  return.  The  patient  is,  however,  greatly  debili- 
tated; headache,  vomiting,  stypsis  and  dyspepsia  continue,  and  frequently  in 
the  period  of  convalescence  death  occurs  suddenly  from  cardiac  paralysis. 

The  urine  frequently  shows  glycosuria,  alimentary  as  well  as  spontaneous. 

How  is  acute  morphinism,  or  opium  poisoning,  to  be  treated  ? 

First,  in  all  cases,  the  stomach  is  to  be  washed  out,  even  though  morphin 
has  been  injected  subcutaneously,  for  it  is  excreted  into  the  stomach. 

The  sopor  must  be  combated;  a  warm  bath  with  cold  affusions  gives  the 
most  certain  results.  If  this  procedure  has  no  effect,  venesection  and  the 
inhalation  of  oxygen  should  be  resorted  to.  In  desperate  cases  tracheotomy  is 
also  to  be  performed,  and  oxygen  may  be  introduced  through  a  tracheal  can- 
nula. If,  as  in  the  case  of  a  child,  respiratory  disturbances  are  most  promi- 
nent, artificial  respiration  and  even  phrenic  faradization  is  to  be  employed. 
Threatening  cardiac  collapse  is  to  be  met  with  injections  of  camphorated  oil 
as  well  as  hypodermics  of  strychnin. 

So  much,  briefly,  in  regard  to  acute  morphin  poisoning. 

A  very  important  role  is  played  by  chronic  morphin  toxicosis,  which 
is  widely  prevalent. 

The  diagnosis  is  not  always  easy,  for  often  the  patient  makes  every  effort 
to  mislead  the  physician.  Numerous  deeply  situated  scars  on  the  skin  from 
abscesses  of  the  subcutaneous  cellular  tissue  are  suspicious.  Dyspepsia,  styp- 
sis, also  the  symptoms  of  marasmus  praecox,  increase  the  likelihood  of  the 
diagnosis,  but  it  becomes  absolutely  certain  only  when  the  patient  confesses 
that  he  uses  morphin,  or  when  solutions  of  morphin  are  found  in  his  possession. 

The  treatment  of  chronic  morphinism  can  be  successfully  carried  out  only 
in  a  hospital  or  in  sanatoria  adapted  to  this  purpose.  A  withdrawal  treatment 
must  be  more  or  less  slow,  according  to  the  somatic  condition  of  the  individual. 
Hitzig's  gastric  lavage  with  Carlsbad  water,  and  the  simultaneous  subcutaneous 
injection  daily  of  decreasing  quantities  of  morphin,  are  advisable.  The  em- 
ployment of  so-called  substitution  methods,  i.  e.,  the  substitution  of  alcohol, 
cocain,  etc.,  for  morphin,  has  produced  no  good  results. 

If,  under  this  withdrawal  treatment,  signs  of  collapse  appear,  the  treatment 


ALKALOIDS  597 

is  to  be  discontinued.  Larger  dose«  of  morphin  must  l>c  administered,  or,  if 
cardiac  weakness  intervene  digitalis  or  subcutaneous  injections  of  camphor- 
ated oil,  etc.,  arc  to  be  employed. 

We  now  turn  to  atropin  poisoning. 

The  cases  of  poisoning  where  atropin  lias  been  administered  as  medicine 
are  very  rare.  Poisoning  by  belladonna  (atropa  belladonna)  is  more  frequent. 
These  cases  of  poisoning  occur  usually  in  children.  The  characteristic  symp- 
toms are  dryness  of  the  mouth,  burning  of  the  throat,  and  difficulty  <>f  deglu- 
tition. There  is  also  extreme  psychical  alteration.  The  cardinal  symptom. 
however,  is  maximal  dilatation  and  absence  of  reaction  of  the  pupils,  accom- 
panied by  marked  acceleration  of  the  pulse.  In  cases  terminating  fatally,  deep 
coma  supervenes,  then  paralyses  of  all  kinds,  and  the  patients  succumb  in  a 
few  hours. 

In  all  such  forms  of  poisoning  immediate  gastric  lavage  is  indicated,  as 
well  as  the  employment  of  emetics,  and  subcutaneous  injections  of  apomorphin. 

The  best  antidote  is  morphin  subcutaneously  injected  in  doses  of  0.0-2-0.03 
gram. 

Among  the  poisons  of  special  interest  to  the  physician  is  that  of  COCAIN, 
an  alkaloid  produced  only  within  the  Last  two  decades  of  the  lasl  century,  but 
which  has  found  employment  in  medicine  to  a  great  extent  as  a  local  anes- 
thetic. Intradural  injections  of  cocain  have  lately  been  advised,  and.  unless 
the  greatesi  care  is  exercised,  these  will  soon  increase  the  numbers  of  poison- 
ings from  thi-  remedy. 

The  first  symptom  of  cocain  poisoning  is  local  anesthesia  of  the  areas  of 
the  body  coming  in  contad  with  the  cocain.  a  symptom  which  the  physician  is 
frequently  desirous  of  producing.  I  fhfortunately  this  symptom  does  not  appear 
alone,  hut  the  respiratory  and  pulse  frequency  are  increased,  arrhythmia  of 
cardiac  action  occur-,  the  pupils  are  dilated,  then'  ig  cyanosis  combined  with 
pallor,  and  the  patient  succumbs  to  cardiac  collapse.  Occasionally  such  cases 
are  characterized  by  the  appearance  of  severe  mental  disturbance  prior  to  the 
final  collapse;  not  rarely,  however,  even  after  these  very  severe  symptoms,  final 
recovery  takes  place.  Treatment:  (la-trie  lavage  if  there  is  Bevere  collapse; 
warm  hath-  with  cold  affusions. 

A  disease  which  ha-  only  lately  originated  from  the  abuse  of  cocain  is 
cocainism,  which,  in  it-  disastrous  consequences,  is  scarcely  less  important  than 
chronic  morphinism;  the  symptoms  are  generally  referable  to  the  nervous 
system,  and  their  numher  is  legion:  rapidly  increasing  marasmus  causes  the 
early  death  of  the  patient. 

In  the  group  of  the  glucocides  only  one  t<.\ico-i-  play-  a  Leading  role,  and 
this  i-  poisoning  from  the  leaves  of  digitalis  purpurea,  which,  as  is  well 
known,  contain-  two  glucocides  (digitalin,  digitalein),  besides  digitonin  and 
digitoxin,  a  soap-like  substance. 

The  curative  effects  of  infusion  of  digitalis  and  tincture  of  digitalis,  etc., 
are  known  to  all  physicians — the  increased  diuresis,  the  stronger  cardiac  con- 
traction, the  Blowing  of  the  pulse.  If  is  perhaps  not  --.  well  known  that  in- 
fusion <.f  digitalis  may  become  decomposed  by  the  action  of  mold  fungi  and 

bacteria   and    toxic   -uh-taiicc-  appear    in  consequence. 


598  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

In  summer  we  should  make  it  a  rule  to  ascertain  that  an  infusion  of  digi- 
talis has  not  decomposed;  but,  besides  this,  digitalis  in  too  large  a  dose,  or  in 
too  large  a  dose  in  a  special  case,  may  cause  symptoms  undesirable  to  both  the 
patient  and  the  physician.  Among  these  we  may  mention  vomiting,  gastric 
oppression,  marked  diminution  of  the  pulse  frequency,  slight  muscular  trem- 
bling, symptoms  of  depression,  irregular  pulse,  cold  sweats,  severe  urticaria- 
like  exanthems.     In  the  severest  cases  death  occurs  in  collapse. 

Mild  cases  run  a  favorable  course  in  a  few  days  without  treatment,  or  by 
simply  stopping  the  administration  of  digitalis.  The  severe  and  most  extreme 
cases  require  active  treatment.  The  stomach  and  intestines  must  be  emptied, 
caffein  and  theobromin  given,  and  serpentaria  virginica  may  be  employed  as 
an  antidote.  If  the  signs  of  cardiac  debility  are  threatening,  strychnin  and 
atropin  are  to  be  subcutaneously  injected. 

I  may  remark  that  severe  forms  of  digitalis  poisoning  are  rarely  observed 
by  the  physician. 

Of  poisonings  with  bitters  and  indifferent  agents,  only  aloin  toxicosis  need 
be  mentioned. 

Employed  in  small  doses  (0.2-1.0  gram)  aloes  cause  copious  diarrheic 
discharges.  Very  large  doses  give  rise  to  gastritis,  enteritis,  and  nephritis. 
Treatment  consists  in  the  administration  of  opiates  and  mucilaginous  drinks. 
The  best  way  to  prevent  poisoning  of  this  kind  is  for  the  physician  to  refrain 
from  prescribing  aloin  in  too  large  doses. 

A  word  in  regard  to  arnican,  the  active  constituent  of  the  tincture  of 
arnica,  from  arnica  montana.  It  was  formerly  medicinally  employed,  but  is 
no  longer  used.  Its  property  of  markedly  irritating  the  skin,  and,  upon  inter- 
nal use,  of  producing  stomatitis,  gastritis  and  enteritis,  has  robbed  it  of  its 
usefulness,  and  I  only  mention  it  at  this  place  to  warn  the  physician  against 
its  employment. 

We  must  now  refer  to  a  long  series  of  vegetable  and  animal  poisons. 

These  are  related  partially  to  poisonous  albumin  bodies,  such  as  toxalbu- 
mins,  phytalbumoses,  etc.,  as,  for  example,  in  some  poisonous  toad-stools,  in 
snake  poison,  in  spider  poison.  They  are  partly  related  also  to  bodies  previ- 
ously unknown  which,  sooner  or  later,  will  be  assigned  to  one  of  the  previously 
described  groups. 

From  the  great  number  of  poisonings  by  these  agents  I  shall  briefly  men- 
tion a  few  which  are  of  special  interest  to  the  physician. 

First  we  shall  consider  poisoning  from  ergot  (secale  cornutum),  the  per- 
manent mycelium  of  claviceps  purpurea.  The  views  of  physicians  are  not  yet 
in  accord  as  to  the  poisonous  principle  of  this  drug.  According  to  Kobert, 
sphacelinic  acid,  cornutin,  according  to  Jacobi,  sphacelotoxin  is  the  toxic  prin- 
ciple. Poisoning,  as  a  rule,  simultaneously  affects  groups  of  persons  who  have 
eaten  food  prepared  with  flour  contaminated  with  ergot.  The  toxicosis  may 
run  an  acute  or  a  chronic  course. 

Acute  ergot  poisoning  runs  its  course  with  vomiting  and  abdominal  pain, 
pain  in  the  epigastrium,  the  chest  and  extremities.  There  are  various  nervous 
symptoms:  above  all,  paresthesia  and  tonic  contractures  of  the  extremities, 
as   well   as   ataxia,  epileptiform   attacks,   and   severe  psychical   disturbances. 


VEGETABLE  AXD  ANIMAL  POISONS  599 

Cyanosis,  diarrhea  and  fever  may  occur.  In  cases  running  an  unfavorable 
course,  the  temperature  falls  in  the  later  stages,  and  severe  syncope  appears. 
The  patient  succumbs  in  a  few  days,  sometimes  even  after  a  few  hours.  The 
prognosis  of  ergotin  poisoning  is  always  grave,  as  the  sequelae  of  such  poi- 
soning, even  in  cases  running  a  favorable  course,  may  be  noticeable  for  years 
afterward. 

For  a  positive  diagnosis  of  the  affection,  ergot  must  be  found  in  the  vom- 
ited material,  in  the  remains  of  the  Hour  which  lias  been  ingested.  For  this 
purpose  we  use  the  coloring  matter  contained  in  ergot — erythrosclerotin. 

Treatment. — As  a  primary  measure  the  proper  instruction  of  the  public 
should  be  enjoined.  The  treatmenl  itself  consists  in  washing  out  the  stom- 
ach, emptying  the  intestine  by  the  employment  of  enemata  or  of  purgatives 
such  as  castor  oil  and  calomel  ;  as  antidotes,  tannin  and  ehlorin  water;  for  the 
collapse,  warm  baths  with  cold  affusions;  in  milder  cases  stimulants,  such  as 
coffee,  tea,  alcohol.  In  severe  cardiac  collapse  injections  of  camphorated  oil 
are  recommended. 

The  phenomena  of  chronic  ergotism  relate  particularly  to  the  nervous  sys- 
tem. The  most  marked  symptoms  are  the  paresthesias,  in  consequence  of 
which  the  disease  is  still  popularly  called  itching  disease  (  Kribbelkrankheit). 
First  tonic,  then  clonic,  spasms  occur  (convulsive  ergotism);  the  patient  ema- 
ciates i"  an  extreme;  trophic  disturbances  of  all  kinds,  such  as  furunculosis, 
loss  of  hair,  loss  of  the  nails,  etc.,  follow.  The  most  dangerous  form  is  that 
known  to  the  physician  as  gangrenous  ergotism.  Gangrene  of  an  extremity 
in  a  short  time  leads  to  septic  infection  to  which  the  patient  succumbs. 

The  treatment  of  the  intestinal  symptoms  is  the  same  as  in  acute  ergotism. 
The  Bevere  pain-  are  relieved  by  sodium  salicylate,  bromids,  and  opiates,  and 
protracted  lukewarm  baths  are  also  beneficial;  gangrene  necessitates  surgical 
measures,  although  they  are  usually  of  no  avail. 

Following  ergotism,  we  musl  consider  pellagra  (mal  de  sol)  «lue  to  the 
ingestion  of  spoiled  maize.  Besides  a  number  of  dyspeptic  difficulties,  an 
erythema  presents  itself  particularly  upon  the  exposed  portions  of  the  body 
and  recurs  year  after  year  in  summer.  The  patient  emaciates,  nutrition  Buf- 
fers greatly,  and  he  becomes  anemic  Nervous  Bymptoms  follow;  pan 
paralyses,  atrophic.-  of  the  musculature,  ptosis,  amaurosis,  etc.  The  patient 
improves  in  winter;  bu1  anemia,  dropsy,  and  finally  fever  and  delirium  often 
Bel  in,  and  after  suffering  for  years  he  succumbs,  provided  an  intercurrent 
affection  such  as  tuberculosis  or  sepsis  does  nol  cause  death  before  this. 

The  prognosis  is  exceedingly  unfavorable,  the  treatment  unfortunately  in- 
effectual, and  only  by  a  proper  prophylaxis  and  the  avoidance  of  spoiled  maize 
as  food  can  we  prevenl  the  appearance  of  this  dreaded  plague.  It  is  endemic 
in  I'liaul  and  upper  Italy  as  well  a-  in  Bukowina. 

Poisoning  by  roAD-8TOOL8  is  of  practical  interest.  We  will  consider  only 
the  amanita  phalloides  and  the  agaricus  phalloides.  These  are  often  con- 
founded with  the  Held  champignons  which  resemble  them.  The  plum  agaricus 
is  the  mosi  frequenl  cause  of  this  form  of  poisoning. 

The  symptoms  are  profuse  diarrhea,  vomiting,  anuria.  Bpasms  and  col- 
lapse, to  whuh  the  patient  may  BUCCUmb  even  in  the  first  stage,     In  the  fur- 


600  IMPORTANT  POISONS  AND  THEIR  TREATMENT 

ther  course  of  the  affection,  jaundice  and  nephritis  occur.  The  disease  is 
very  serious.  Seventy-five  per  cent,  of  those  attacked  die.  Treatment :  Gas- 
tric lavage,  venesection  with  subsequent  salt  infusion,  and  subcutaneous  injec- 
tion of  strychnin. 

Poisoning  with  agaricus  muscarius  must  also  be  considered.  The  symp- 
toms are  vomiting,  hemorrhagic  diarrhea,  a  condition  resembling  alcohol  in- 
toxication, followed  by  tonic  and  clonic  spasms  to  which  the  patient  may  suc- 
cumb in  a  few  hours  or  a  few  days.  The  prognosis  is  decidedly  more  favorable 
than  in  poisoning  with  agaricus  phalloides.  Treatment :  Gastric  lavage, 
emetics,  apomorphin,  then  tannin;  perhaps  also  venesection  and  normal  salt 
infusion. 

In  poisoning  with  iiebeloma,  on  account  of  the  muscarin-like  effect,  injec- 
tions of  atropin  are  in  place. 

We  must  still  refer  to  poisoning  with  mushrooms.  The  edible  mushroom 
is  non-toxic.  All  poisonings  of  this  kind  are  due  to  the  toxic  mushroom, 
which  greatly  resembles  it. 

The  symptoms  are  similar  to  those  produced  by  amanita  phalloides.  But 
the  course  is  generally  more  favorable  and  briefer.  The  treatment  is  the  same 
as  in  poisoning  with  amanita  phalloides. 

It  must  be  borne  in  mind  that  non-toxic  mushrooms  may  also  give  rise 
to  poisoning,  if  they  have  decomposed.  The  best  prophylaxis  against  mush- 
room poisoning  is  proper  instruction  at  school  in  the  recognition  of  the  poison- 
ous mushrooms ;  the  inspectors  in  markets  should  by  strict  supervision  prevent 
the  sale  of  the  toad-stool  which  so  closely  resembles  the  non-toxic  mushroom. 

In  discussing  fish  poisoning  we  may  be  brief.  It  is  of  but  little  conse- 
quence. If  the  fish  itself  is  non-poisonous,  poisoning  is  only  brought  about 
by  the  fact  that  it  was  already  decomposed  when  eaten.  Such  poisoning  will 
be  included  under  meat  poisoning. 

Fish,  however,  may  be  poisonous.  For  example,  eel  blood  is  poisonous,  the 
roe  of  the  barbel  and  of  the  pike  (esox  lucius)  contains  toxic  substances,  and 
this  is  also  said  to  be  true  of  the  head  of  the  sheat  fish  (silurus  glanis).  The 
tetrodon  varieties  indigenous  to  Japan  contain  a  poison  resembling  curare. 
The  ingestion  of  fish  may  also  have  a  deleterious  effect  if  the  fish  itself  has 
been  diseased  (bacillary  infection,  plasmodia,  invasion  of  entozoa).  The  his- 
tory will  for  the  most  part  point  to  the  diagnosis.  The  symptoms  are  mani- 
fold; usually  the  signs  of  gastritis  toxica  dominate  the  situation,  but  nervous 
phenomena  such  as  pupillary  symptoms,  spasms  and  unconsciousness  also 
appear.  The  course  of  the  disease  is  generally  severe,  and  frequently  the 
termination  is  fatal. 

The  treatment  consists  in  gastric  lavage,  the  earlier  performed  the  better; 
but  this  should  also  be  employed  in  the  later  stages  if  vomiting  is  present. 
Toxic  gastroenteritis  is  to  be  relieved  by  opiates  and  mucilaginous  drinks. 

Oysters  and  mussels  may  produce  similar  effects,  if  the  bivalves  were 
themselves  diseased,  or  had  fed  on  poisonous  substances. 

In  conclusion,  we  proceed  to  the  discussion  of  meat  poisoning. 

Although  the  various  forms  of  meat  poisoning  differ  in  their  etiology, 
there  is  but  little  difference  in  their  pathology;  they  may  be  due  to  eating 


VEGETABLE   AND  ANIMAL   POISONS  601 

poisonous  animal  food  or  the  meat  of  diseased  animals.  We  shall  investigate 
particularly  that  form  produced  by  the  ingestion  of  decomposed  meat  of  any 
kind.  This  we  usually  designate  as  alantiasis  or  botulism.  This  form  is  the 
most  important,  as  it  is  the  one  mosl  frequently  observed  by  the  physician. 

We  must  distinguish  three  quite  different  clinical  forms:  (a)  That  form 
which  presents  predominant  paralytic  symptoms;  (b)  that  form  running  its 
course  with  symptoms  of  atomatropin  poisoning;  (c)  that  form  running  its 
course  with  symptoms  of  gastroenteritis.  The  ingestion  of  decomposed  sausage, 
in  particular,  causes  the  second  form,  while  the  ingestion  of  liver  and  kidney 
causes  the  gastroenteritic  symptoms. 

The  affection  is  always  to  be  regarded  a>  serious;  the  mortality  is  very  high. 

The  treatment  must  be  in  accordance  with  the  form  of  the  intoxication. 
In  any  case,  the  immediate  washing  out  of  the  stomach  is  always  in  place. 
The  treatment  of  the  second  form  is  the  same  as  thai  of  fish  poisoning,  while 
in  the  third  form  the  treatment  of  gastroenteritis,  repeatedly  mentioned,  is 
here  of  the  utmost  importance.  In  conclusion  it  must  be  home  in  mind  that 
other  foods  also,  such  as  milk  and  cheese,  may  be  the  cause  of  similar  poisoning, 
and  poisoning  after  the  ingestion  of  foods  containing  vanillin  may  he  included 
in  this  category. 


INDEX   OF   AUTHORS 


Abel,  210. 
Abelous,  205,  206. 
Addison,  199,  200,  202,  205,  214. 
Adrian,  C,  253,  259. 
Ajello,  459,  494. 
Albarran,  449,  513. 
Albu,  14,  40. 
Alexander,  209. 
Allen,  513. 
Ammann,  E.,  419. 
Ammon,  514. 
Anderson,   !  12. 
Andersson,  225. 
Anger,  518,  519. 
Anschütz,  W..  246,  259. 
Arctander,   182. 
Arnold,  235,  237,  327,  347. 
Arstan,  563. 

Askanazt,  347,  376,  386,  512,  545,  553,  554, 
■".".7,  558. 

AtTLEE,     I'll. 

A  l  WATER,    20.    2  I. 

Auld,  204. 

AVERBBCK,    _'l  1. 


B 

Babcock,  i(.t.">. 

Babes,  216,  394,  KX),  129,  WO. 

Bacceij  i.  533 

Bachstrom,  397. 

Bai  i/.  506,  510,  511,  549. 

I'm-«  H,   .".17. 

Bamberg]  r,   168,   176. 
Ban«  ftO]  i,  .".  16,  •">  17. 
Bang,  266,  267. 
Bannattni,  243,  255,  259. 


Banti,  382,  383,  384,  386. 

Banting,  70,  72,  73,  74,  163,  164,  165,  166, 

173,  175. 
Baraban,  506. 
Barjon,  257,  259. 
Barlow,  485. 
Barszewsky,  271. 
Batemann,  459. 
Batsch,  516. 
Bauer,  39. 

Baumann,  2,  189,  190,  191. 
Bäumler,  l>  i:;.  247. 
Bavay,  54  !.  545. 
Bazi.v,  1  i:;. 

Bechterew,  246,  247,  259. 
Beckler,  397. 
B]  i  Qi  i  im  i  .  334,  341,    108. 
Beer,  248,  259. 
Behla,  506. 
Benda,  C,  229. 
\  \\   Beneden,  526. 
Benedict,  20,  24. 
Bennecke,   I!..  _'I7. 
Hi;o\\  ii .  .".  13. 
Mi  i.i  \i.    \\  ..  256,   _'C,(). 
Bbrgell,   18,  266. 

Bernard,  Clai  db,  mi.  im,  i  15,  no. 
Bi  i  ri  Mm  im  ,   [89. 
Bial,  263,  _'«V7.  269,  _'7().  271. 
Bidder,   l.  10. 
Biedert,   17. 
Hum.,  208. 

Bn  i.-.  Augi  -i.  258,  259,  260, 
I'.n  i.mi  i:.  509. 
I'm  ii  irz,  512,  .".Co. 
I '.i 1 1  in..-,   195,  556, 
Billroth,  378,  inn. 
r.iNi  i,  3o. 

Biiicii-llii;-.  hi  n  i..    I  ; 3 


604 


INDEX  OF  AUTHORS 


BlRCHER,    188. 

Bischoff,  E.,  4,  56. 

Bitter,  542. 

Bjierre,  89. 

Blanchard,  515,  516,  521,  544,  564. 

Bland-Sutton,  506. 

Blaschek,  535. 

Blaxall,  255,  259. 

Bleibtreu,  56. 

Bloch,  516,  519. 

Blum,  189,  209,  226. 

Blumenthal,  F.,  262,  269. 

Bobrizki,  469. 

Boer,  219. 

Boerhaave,  162. 

BOHLAND,    563. 

Bollinger,  415. 

Bonfils,  370,  386. 

bontekoe,  391. 

Bornstein,  19,  20,  56,  57. 

Bornträger,  394. 

Bostroem,  509. 

Bouchard,  Ch.,  22,  26,  33,  143,  243,  252, 

255,  257,  260. 
Boursier,  449. 
Bozzolo,  560,  564. 
Bramwell,  Byrom,  180,  185,  195. 
Brandenburg,  286 
Brat,  270. 
Brauer,  573. 

Braun,  G,  511,  512,  515,  520,  575,  576. 
Braun,  Julius,  246,  260. 
Brehmer,  63. 
Breisacher,  14. 
Breithaupt,  14. 
Bremser,  520,  565. 
Brieger,  531. 
Brillat-Savarin,  170. 
Brock,  513,  514. 
Broden,  25. 
Broock,  454. 
Brown,  303. 

Brown-Sequard,  205,  206. 
Bruce,  195. 
Brunner,  534. 
v.  Bruns,  192,  193,  534. 
Bryant,  531. 
Buhl,  433. 

Bunge,  153,  154,  155,  398,  410. 
Bunsen,  586. 
Burchard,  553. 
Burmeister,  572. 


Burresi,  216. 
Busk,  510. 


C 


Cabot,  194,  195,  283,  366. 

Camerer,  36,  37. 

Canard,  286. 

Cannstatt,  470. 

Cantani,  98,  164,  165. 

Caporelli,  271. 

Caspari,  18,  20,  38,  51. 

Casper,  L.,  451. 

Cassirer,  R.,  248,  260. 

Castan,  450. 

du  Castel,  463. 

Ceci,  460. 

Celsus,  175,  389. 

Chalvet,  408. 

Chambers,  Thomas  K.,  163,  165. 

Charcot,  140,  179,  243,  244,  245,  246,  248, 

250,  522. 
Charles,  545. 
Charrier,  256. 
Charrin,  260. 
Charron,  482. 
Chelius,  415. 
Chenzinsky,  295. 
Chossat,  4. 
Clark,  335,  386. 
Clarke,  I.  L,  247,  260,  506. 
Cobbold,  504,  510,  511,  521,  546,  547. 
Cohen,  G.,  425,  435. 
Cohnheim,  J.,  370,  386,  424,  558. 
colombini,  271. 
Contu,  394. 
Cordus,  390. 
Cornet,  296. 
Cremer,  18. 
Cunier,  421. 
Cunningham,  190,  507. 
Curschmann,  H.,  246,  260,  303. 
Curtis,  571. 
Cybulski,  205,  208. 
v.  Cyon,  208. 


D 


Daday,  520. 
Daniels,  517. 
Dapper,  56,  73. 
Dare,  A.,  277. 


INDEX  OF  AUTHORS 


605 


Darier,  208. 
Darwin,  418. 
Davaine,  G.,  244,  260,  504,  507,  517,  521, 

534. 
Da  vies,  Y.,  194. 
Debove,  161. 
Deffke,  515. 
Dehio,  504,  523. 
Delpech,  A.,  126,  397. 
De.ma.ntke,  539. 
De.marquay,  546,  547. 
Demme,  460,  549. 
Demys,  460. 
Dexti,  504. 
Desnob,  4.51. 
Dettweiler,  63. 
Deucher,  46,  47,  48. 
Diesing,  510,  546. 
Dock,  507. 
Dohrn,  468. 
DE   Domexicis,   205. 
DONDEBS,    166. 

IiuMiiivxis,  390. 

Donne,  507. 

Dörixg,  391. 

Drawitz,  390. 

Dbechsel,  189. 

Dryer,  208. 

Dubini,  553,  560. 

Duchek,  408. 

Duckworth,  Sir  Dyce,  128. 

Duces,  565,  566. 

DUHRING,     170. 

Dujardix,  507,  516,  544. 
I)i  NSCHMANN,    40. 

v.   Du»  ii.    It,:;,    im),  492,  493. 
Duval,  510. 

E 

Ebstein,  W.,  56,  70,  72,  73,  74,  125,  151, 

152,  L67,  -'l  l,  355,  375,  386. 
Echthh  8,  390. 

I  ;•  i.i  KB  wi/.   507. 
I  .<  KB  \i:i>.    I  1  (,    115. 

Edel    225. 

I'.nw  LRD6,   313. 
EhBENBI  BO,   ■"■')7. 

Ehrhabdt,  113. 

iJiKi.i.  ii,  1'.,  293,  294,  295,  300,  304,  305, 

319,  345,  3i.,.  317,  351,  354 

37.V  376,  377.  384,  387. 


ElCHHORST,    39. 

Eisexi.ohh,  .523. 

Elter,  J.,  259,  260. 

Excel,  C.  S.,  286,  347. 

Epstein,  507,  548. 

Erb,  242. 

Ebben,  47. 

Eryaxt,  563. 

Eschle,  596. 

Eugalexus,  390,  391. 

Eversmaxx,  572. 

Ewald,  C.  A.,  179,  180,  190,  193,  194,  212. 


F 

Fabbicius,  .566,  574. 

Fauvel,  396. 

Federolf,  553. 

Feilchexfeld,  L.,  269. 

Ferria,  195. 

Fischer,  Emil,  265. 

Fischer,  M.,  416,  423,  435,  520,  569. 

Fi.eixer,  216,  220. 

fxeischeb,  42,  353. 

Fleische,  277. 

Flemming,  565. 

Flesch,  239. 

Fleuby,  386. 

Fi.exxer,  505. 

Flodeim  s.    117. 

Fol,  209,  219. 

Fordyce,  437. 

Forster,  8. 

Fox,  510. 

Francoi  pe,  56  I. 

Frank.  Johann  Peter,  144,  160,  162. 

Fbänkel,  A..  130.  210,  ■s;:;.  355. 

Ii:  \)  NKEL,    8.,     IV. 

Fbebichs,   10. 

Fri  I   DWI  III  i:.    37l'>,    3s7. 
1'i;ii:i.i:i  SO]  :;.   .510. 

I " i . 1 1  i > i  n  i  ii  \i .  266. 

l'i  II  BBOBN,  518. 

l'i  i:  -i  I  M-.I  BO,   .507. 
v.    Fi  i;m.   210. 

G 

<  i  Mi:  l  M  l:.    _'70. 

Qaj  i  n.  545. 

< ;  \m  ind-Gu  i/i .  1 1'». 

GARRB,   .531. 


606 


INDEX  OF  AUTHORS 


Garrod,  128,  132,  136,  146. 

Garrod,  Alfred,  243,  255,  260,  398,  410. 

Garrod,  Archibald,  243,  257,  260. 

Gärtig,  H.,  39. 

Gärtner,  429,  486. 

Gauthier,  195. 

Gavoy-Ritter,  424. 

Gayet,  441. 

de  Geer,  566,  571,  573. 

Geigel,  124. 

Gendre,  460. 

Geppert,  8,  27,  34. 

Gerhardt,  38. 

Gerhardt,  O,  253,  256,  260,  342. 

Gerhardt,  D.,  110. 

Gervais,  566,  569. 

Giesker,  510. 

Gilbert,  A.,  144. 

GlNNARD,    460. 

Giovannini,  429,  460,  463,  489. 

Gley,  187. 

Gocht,  417,  432,  439,  440,  441,  455,  456. 

Goeze,  514,  517,  565. 

goldmann,  190. 

Golowin,  535. 

Gottlieb,  190,  208. 

Gottstein,  195. 

Grandidier,  414,  415,  417,  422,  424,  452. 

Grassi,  503,  507,  516,  517,  523,  545,  546, 

548,  550. 
Grassmann,  48. 
Gratiolet,  205. 

Grawitz,  E.,  29,  320,  328,  387,  424. 
Green,  463. 
Greenfeld,  180. 
Greenhow,  214. 
Gretsel,  381,  387. 
Griesinger,  381,  560. 
Griffouillkres,  119. 
Grisolle,  459. 
Gros,  505. 
Grosglik,  S.,  444. 
Gruber,  13. 
Grund,  266. 
Grünig,  543. 
Gubler,  239. 
Guelliot,  482. 
Gull,  Sir  Wm,  179. 
Güterbock,  535. 
Guthrie,  451. 
Guyon,  450. 
Guyot,  455,  546. 


H 

Hagler,  157,  158. 

Hahn,  542. 

Haldane,  328. 

Hamm,  245. 

Hammarsten,  265. 

Hammerschlag,  284. 

Hamonic,  449. 

Hanau,  233,  239,  241. 

Hanot,  460. 

Hansemann,  239,  241, 

Harley,  205,  394,  513. 

Harris,  445. 

Harrison,  513. 

Hartmann,  551. 

Harvey,  70,  72,  163,  165. 

Hayem,  465,  488. 

Heberden,  248. 

Hebra,  470. 

Heidenhain,  347. 

Heinsheimer,  180. 

Helmholtz,  2. 

Hemard,  454. 

Henle,  536. 

Henneberg,  19. 

Hennig,  190. 

Henoch,    403,    404,    479,    481,    482,    485, 

497. 
Hermann,  566. 
Hertoghe,  192,  194. 
Hertwig,  O.,  418. 
Herve,  482. 
Herz,  251,  260. 
Heubner,  36,  47,  486. 
Hewes,  283. 
Heyland,  424. 
Heymann,  R.,  454. 
Hilton,  J.,  553. 
Hinsworth,  542. 
Hippocrates,  147,  166,  389,  473. 
Hirsch,    August,     389,     390,     391,    397, 

398. 
Hirsch,  Th.,  441. 
Hirschfeld,  F.,  14,  40,  56,  70,  72,  73,  74, 

174. 
His,  Jr.,  130. 
His,  W.,  243,  417,  418. 
Hitzig,  596. 
Hochs,  480. 
Hodgkin,  370. 
Hofbauer,  446. 


INDEX  OF  AUTHORS 


607 


Hoffa,  256,  260,  439,  455,  456. 
Hoffmann,     Albin,    88,    243,    253,    260, 

424. 
Hofmeister,  3    190,  196. 
Home,  395. 
Hooper,  423. 
Höpfxer,  558. 

Hoppe-Seyler,  1,  8,  36,  49,  505. 
Horsley,  189. 
Hösli,  417. 

v.  Hösslin,  23,  48,  175,  176. 
Huber,  538,  549,  576. 

HtLTGREN,    225. 

Hun,  185. 

hundhausen,  johannes,  167. 

HtTNSCHE,    570. 

Hutchinson-,   Woods,  241. 
Hyrtl,  152. 


Ijima,  505,  521. 

Immermann,  164,  406,  425,  427,  432. 
Israel,  J.,  445,  446,  451. 
Israel,  O.,  234,  240. 


Jackson,  394. 

Jacob,  18,  266. 

Jacobi,  207,  598. 

Jacoby,  508,  563. 

v.  Jaxsch,  I!..  382,  387,  408,  579. 

Janowski,  507. 

,I\\ /.in.    120. 

Jaqi  ii.  34,  35,   190. 

.1  UM  ROWITZ,    'Jliti,    •_'(')<). 

Jenkins,  531. 
Johnston,  565. 
JoiNvn .i.i  .  390. 
Jolles,  A  .  374,  387. 
Jones,  Lloi  d,  33 1.   160. 
Joseph,  572. 
Ji  i;.,i  ns,  216,  508,  535. 


K 

Kachel,  If.,  249,  260. 

v.   Ka i  n.  213,  216. 

Kahler,  115. 


Kalindero,  216. 
Kaltenbach,  494. 
Kannenberg,  507. 
Kaposi,  479. 
Karewski,  542. 
Karpelles,  565. 
Kartulis,  505,  506,  513. 
Kast,  186. 

Katzenstein,  24,  27. 
Kaufmann,  18. 
Kayseh,  18,  21. 
de   Keersmaecker,    1  17. 
Kehrer,  435,  454. 
Kerbert,  510. 
Ki  dd,  433. 

KlSCH,  70,  72,  73,  74,  177. 
Kjeldahl,  447. 

Klebs,  235,  238,  408,  418,  460. 

Klehmet,  539. 

Klemm,  528. 

Klempeher,  G.,   14,  31,  39,  40,  443,  451. 

Knapp,  268. 

Kobert,  598. 

Koch,  Robert,  275,  290,  292,  460,  461. 

Koch,  W..  127,   128,   129,  430. 

Kocher,   187. 

Kocher,  Jh.,  189. 

Koehler,  Armin,  462. 

v.   Kogerer,  463,    164,  465,  488. 

Koi.h,  489. 

Koi.i.ikkk,  317,  418. 

König,   F.,    132,    138,   139,  440,  455,  456. 

Koppe,  287. 

korktjnoff,  10. 

KossEii,  A..  265,  266. 

Kb  \mi br,  391. 

Krämer,  535. 

Im;  \  i/.  556,  557. 

Kraus,  Fr.,  27,  28,  30,  33. 

Kraoss,   163. 

Kl;  \:    l  Nil:.    573. 

Krebel,  392,  396. 
Kremer,  0.,  256,  260. 

I\i:i  rSCHY,     K|S 

Kim ■■;.   B.,   L5,  16,  17.  19,  56,  57,  81. 

Km  ki  n  in  BO,  -<»«.». 

Ki  ii n.  544 

Külz,   112,  268. 

kumaoawa,   ii. 

Ki  ni.iim.  375,  387. 

Künstle,  39,  507. 

Ki  RIMOTO,   521. 


608 


INDEX  OF  AUTHORS 


Laband,  262,  268. 

Laboulbene,  408,  574,  566. 

Lambl,  507,  565. 

Lancereaux,  243,  252,  257,  260. 

Landau,  197. 

Landre-Beauvais,  243,  260. 

v.  Langer,  229,  230,  235,  238. 

Langerhans,  555. 

Langlois,  205,  206. 

Larrey,  151. 

Laudon,  570,  575. 

Lauenstein,  442,  506. 

Laves,  28,  33. 

Lavoisier,  2. 

Lazarus,  A.,  275,  304,  319. 

Lebreton,  460,  462,  468. 

Lee,  397. 

Le  Gendre,  128,  460. 

Legg,  Wickham,  433,  453. 

Leguen,  442,  448. 

Lehmann,  C.  G  ,  10,  32. 

Lehne,  539. 

Leichtenstern,  29,    194,    545,   549,   560, 

562,  563,  564. 
Leidy,  546. 
Leishman,  292,  296. 
Leloir,  463,  464,  465,  488. 
Lennander,  447. 
Lennhof,  540. 
Leo,  28,  33. 
Leon,  163. 
Lepine,  262. 
Letzerich,  460,  461. 
von  Leube,  303,  344. 
Leuckart,    R.,    506,    509,   510,   514,   516. 

521,  526,  545,  549,  550,  553,  555,  565, 

576. 
Leuthold,  474,  479,  493. 
Levinsen,  560. 
Levy-Dorn,  195. 
Lewandowski,  208,  226. 
Lewin,  G.,  214,  219. 
Lewis,  508,  546. 
v.  Leyden,  39,  40,  443,  506. 
Lichtenfeldt,  20. 
Liebermeister,  25. 

von  Liebig,  Justus,  2,  3,  4,  50,  51,  398,  447. 
Lind,  391. 

Lindemann,  258,  260,  506. 
Lindner,  508. 


Linne,  508,  548,  550,  565,  566,  572. 
Linser,  440. 

v.  Linstow,  516,  518,  519,  546,  547,  549, 
556,  558,  564. 

LlPMANN-WuLFF,    39. 

Liston,  423. 

Litten,  M.,  388,  465,  507. 

Lockwood,  461. 

Loeffler,  291. 

Loesch,  505. 

Loewi,  51. 

Loewy,  A.,  25,  196,  286. 

Lohse,  25. 

Longcope,  365,  371. 

Loos,  503,  512,  513,  514,  546,  562. 

Lossen,  415,  424. 

Loumeau,  449. 

Löwit,  356. 

Lücke,  172. 

Ludwig,  1. 

Luff,  128. 

Lussano,  563. 

Lüthje,  16,  17,  18,  19,  21,  40,  41,  56,  57, 

265. 
lütkemüller,  543. 
Lutz,  503,  548,  553. 
Luzet,  460. 


M 

Mabille,  192. 

Mabon,  195. 

Mackenzie,  189. 

Madden,  Cole,  513. 

Madelung,  534,  537. 

Magnus,  390. 

Magnus-Levy,  A.,  23,  27,  28,  29,  30,   33, 

34,  35,  64,  130,  185,  192. 
Maguire,  535. 
Maillard,  L.,  257,  260. 
Malherbe,  448,  510. 
Malmsten,  508. 

Manasse,  K,  209,  245,  261,  533. 
Mangold,  528. 
Mann,  51. 
Manson,  546,  547. 
Maragliano,  495. 
Marchand,  206,  507. 
Marfan,  460. 
Mari,  394. 


INDEX  OF   AUTHORS 


609 


Marie,  Pierre,  229,  230,  232,  237,  238, 

240,  241,  243,  244,  246,  256. 
Marinescu,  237,  238. 
Marischler,  43. 
Marquardsex,  E.,  167. 
Marro,  551. 
Martixeau,  531. 
Marx,  504. 
Masuts,  564. 
Matthes,  M.,  167. 
Mathieu,  117,  468. 
May,  30,  40,  507. 
Maydl,  536. 
McConnell,  508. 
McKenzie,  D.,  454,  463. 
McLennan,  190. 
M<  Munn,  209,  212. 
Megnin,  566,  569. 
Mehlis,  560. 
Meigen,  574. 
Mi: inert,  323,  335. 
Meischer,  277. 
Melnikoff,  516. 
M  i:\cke,  560. 
Mendelsohn,  261. 
Menzer,  257,  260. 
v.   Mf.kixg,  24,  25,  48. 
Mkkhett,  572. 
Meyer,  Fritz,  270,  271. 
METER,  R.,  2,  33. 
MlESCHER,    506. 

Mikulicz,  193. 
Miller,  394. 

Mm  ii i.i  i..  S.    Wim,  58,  65,  66. 
Miura,  507. 
Miyake,  569. 
M <  > i -. i '  9,  6  J. 
Mokoi  I  ,  '■>  17. 

MÖLLER,     1*5. 
MONK»,    565. 

Moore,  208. 

MoOBBRtTGOER,   553. 

Mm:  UEEWBKI,    17. 

Mo si. eh,  531,  549,  560,  576. 

Mi  mim  \\\,  209. 

Mi  llbb,  I'h..  29,  31,  39,   45,    W,   47,  61, 

64,  266,  528. 
Mi  ii  er,  Joh.,  246,  260. 
Mi  i.i.i- 1:.  W..  259,  260. 

Mi  RRAY,    189. 

Mi  rei,  393,  394 

Mi   r/.i.M'.i .«  HER,    I L5. 
40 


N 
Nasse,  415. 

Naunyn,  B.,  31,  39,  77,  265,  446. 
Neale,  411. 
Nebelthau,  31. 
Nehring,  27,  28,  33. 
Neisser,  536. 
Nettleship,  494. 

Neuberg,  Carl,  265,  266,  267,  268,  269. 
Nettmann,  H.,  265,  260,  267,  347,  354,  363, 

461,  486,  487. 
Xki  sser,  203,  220. 
Newport,  565. 
Nichols,  454. 
Nicolaier,  A.,  148. 
Xie.meyer,  Felix,  340. 
Xitzsch,  569. 
Noll,  265. 
Nonne,  558. 
v.  Noorden,  C,  15,  16,  28,  34,  35,  37,  38, 

39,  40,  41,  42,  47,  54,  56,  68,  72,  73, 

74,  194,  323,  334. 
nordenskjold,  411. 
Nordmann,  514. 
Xoumaxd,  544,  545. 
Nothnagel,  205,  213,  335. 
Ntjtall,  571. 

O 

Oertel,  56,  70,  72,  73,  74,  75,   174,   175, 

425,    127,    132. 
Oestreich,  2'_'4. 
Olaus,  390. 

Ouver,  Thomas,  131,  207,  277. 
O'Neill,  John,  5  18. 
Opitz,  408. 

Ord,  William,  17'.».  184,  L85 
Osler,    William,     151,    283,    382,    383, 

387. 
Os*  M.n,   189,  190. 
Otani,  511. 

«mi.     12  1. 

Otto,   H5 
Owen,  553. 
Ozarkibwicz,   13. 

(  )/./  \i;i»,    ">  17. 


Pan»,  546. 

I'mii  mii  im.  :;i7 


610 


INDEX  OF  AUTHORS 


Park,  196. 

Parona,  545,  560. 

Pasteau,  450. 

Peiper,  E.,  501,  576. 

Pel,  180,  375,  387. 

Pelczynski,  549. 

Penzoldt,  353,  408. 

Pepper,  221. 

Pericic,  541. 

Perroncito,  509,  560. 

Peschel,  14. 

Petrone,  460. 

v.  Pettenkofer,  4,   7,   33,   36,    154,   352, 

353. 
Pfeiffer,  E.,  19,  248,  261. 
Pflüger,  E.,  1,  15,  16,  18,  19,  20,  22,  38, 

41,  50,  57,  447. 
Philippeaux,  205. 

PlCHLER,    528. 
PlCKARDT,    226. 

Picque,  446. 

Pinkus,  375,  376.  377,  3S4,  387. 

Playfair,  58,  65,  66. 

Pliny,  163,  389. 

Poirier,  446. 

Poncet,  A.,  257,  261. 

Ponfick,  186,  196,  242. 

Poppe,  544. 

Portschinsky,  574. 

Posadac,  536. 

Posselt,  528,  529. 

Potain,  224,  253,  261. 

Potal,  257,  261. 

Pousson,  446,  449. 

Pribram,  243,  244,  246,  251,  255,  256,  259, 

261. 
Pröscher,  290. 
Prout,  96. 
Prudden,  185. 
Pruner,  560,  570. 
purinton,  208. 
Putnam,  James  J.,  314. 


Q 


Quenu,  195. 

Quincke,  112,  341,  505. 


R 

Rabinowitsch,  H.,  251,  261. 
Raelmann,  570. 


Raillet,  510,  515. 

Rainey,  506. 

Rayer,  470. 

Raymond,  214. 

Reale,  271. 

v.  Recklinghausen,  427,  465. 

Reclus,  195. 

Redi,  572. 

Redon,  515. 

Reed,  Dorothy,  371. 

Reed,  M.,  387. 

Regnier,  446. 

Reher,  460. 

Reich,  535. 

Reinbach,  193. 

Reinhold,  195. 

Reiss,  L.,  199. 

Renaut,  213. 

Reverdin,  187. 

Reyher,  504,  523. 

Ribot,  418. 

Richter,  196. 

Rieder,  322,  347. 

Riehl,  213,  463,  464,  465,  488 

RlEMANN,    531. 

Riethus,  27,  30. 
Riley,  571. 
v.  Rindfleisch,  359. 
Ritter,  42. 

RlVOLTA,   511. 

Roberts,  127,  137. 
Robin,  A.,  30,  157,  164,  522. 
Robinson,  262. 
Rodier,  334,  341,  408. 
Roese,  250,  261. 

RÖHMANN,    18. 

Rohnstein,  319. 
Rollo,  87. 
Roma,  257,  261. 
Romanowsky,  292. 
Romme,   271. 
Ronsseus,  390. 
Roos,  189,  505,  507. 
Roque,  244,  256,  261. 
Rosemann,  R.,  42,  50. 
Rosenberg,  506. 
Rosenell,  394. 
Rosenquist,  39. 
Rosin,  262,  268. 
Rositzki,  191. 
Rost,  18. 
Rovighi,  533. 


INDEX   OF  AUTHORS 


611 


Rovblng,  447,  448. 

Rubexsteix,  347,  365,  366. 

Rubner,  2,  3,  4,  5,  6,  9,  12,  21,  23,  34,  36, 

37,  44,  47,  98. 
Rudolph,    510,    514,    516,    517,   546,    548, 

552,  560,  570. 
Riff.  264. 
Runeberg,  504,  523. 

RUPPRECHT,    556. 


Sabatier,  442. 

Sahi.i,  279,  425. 

Saint-Remy,  506. 

Balis,  541. 

Salkouski,   E.,   262,   263.   265,   266,   267, 

269,  272. 
Salomon',  25. 
S wusch,  567. 
San  Tim,  533. 
Savage,  180. 
Savenzy,  419,  565. 
SCANZER,   543. 

Schäfer,  207. 
Schapiro,  111,  504,  523. 
Schatten  froh,  25. 
Schatz,  543. 

Sriiu'hiw,  .-»im;.  508. 

BCHAUMANN,    319,   504,   523. 

Scheby-Buch,  458,  477. 
Schede,   1 1_'. 
Si  iiii  m:.  .".17.  548. 
Schiassi,  I'...  386,  387. 
Schiff,  M..  187,  188,  205. 
S<  mi  h.   Walter,  379,  387. 
S.  im. i. in.;.   225. 

Schlei«  h,  58  L 

Schlesinger,  _'  17,  261 . 

Schm  \i.i/,  284. 

Schmidt,  Ad.,  4,  10,    15,    W,    17,    18,  507, 

543. 
Schmidt,  Alex.,   124. 

ScilMIl   hi   l:l   RG,    •'!  12. 

Schmitz,  80,  81. 

S.  BMOLL,     l_'. 

Schneider,   108,  544, 

Siiim  i /i  i  i;.   .".  I  1. 

Scholz,  '-".». 
Schönfeld,  542. 

BCHÖNLEIN,  I.".  I.  157,  170,  173,  171.  17.".. 

176,  177,  178,  I7'.t. 


Schrank,  565. 
Schreiber,  E.,  169. 

SCHRÖDT,  194. 
ScHUBERG,  507. 

Schubert,  43. 

SciIUCHARDT,    250,    261. 

Schiller,  M.,  243,  244,  255,  261. 

Schi- Liz K.  .Max.  347,  543. 

Schürmater,  507. 

Schüssler,  536. 

Schwab,  459. 

Schwalbe,  167. 

Schweninger,  70,  75. 

Schwimmer,  458. 

Scrlba,  569. 

Sedan,  419. 

Seggel,  407. 

Senator,  H.,  115,  226,  243,  248,  261,  370, 

387,  442,  443,  446,  447,  451. 
Senn,  369. 
Serrano,  189. 
Shaw,   179,  565. 
v.  Siebold,  510,  516,  526,  570. 

SlGNORET,    .->72. 

Silbermann,  462,  463,  464,  495. 
Simmons,  371. 
Simon,  556,  569. 
Simon-Legrain,  460. 

SlVEN,    1  f,    15. 

Sealler,  7.117. 
Smith,  328. 
soennecken,  276. 
Sond]  \.  36,  37. 

SONSLNO,    513. 

Speck,  25. 
Sperling,  549. 
Spie  rscHB  \.  495. 
Si  Mci.1.,   193. 
Stadi  im  \\\,  •".  I.  _'■'.  I. 
Si  \i.ni  \.,i  n.  353. 
Sa  \in  I..    1 17.. 

Sil  i\  BACHER,   .1.,    17  1. 

Steinbi  so,  508. 
Sn  i\ brI  i  k.  535. 
Stengel,  320. 
Stepp,  540. 

Sternbi  rg,  229,  230,  231,  _'.;:..  234,  235, 
_'.:••,.  230,  240,  241,  387,  505. 
v  366. 
Stetskal,    17. 
Siii  i  b,  503,  506. 
Si...  k\  i-.  508. 


612 


INDEX  OF  AUTHORS 


Stoermer,  113. 

Strassburger,  J.,  46,  48. 

Strauss,  H.,  47,  112,  257,  261,  319,  361. 

Streng,  507. 

van  der  Stricht,  Claus,  239. 

Stroganow,  465,  488. 

Ström,  482. 

Strube,  507. 

Strubell,  113,  120. 

Strümpell,  39,  236,  246,  436. 

Stüve,  27,  28,  33. 

Subboitic,  541. 

Sudeck,  251,  261. 

Svenson,  27,  32,  34. 

Sydenham,  Thomas,  126,  147,  340,  391. 

szkekeres,  535. 

Szymonowicz,  205,  208. 


Tallermann,  258,  261. 

Tallquist,  21,  277,  523. 

Talma,  386,  387. 

Tambach,  189.  * 

Tamburini,  239,  241. 

Targeff,  506. 

Tedenat,  449. 

Teissier,  244,  256,  261,  545. 

Terillon,  534. 

Terrier,  118. 

Tham,  507. 

Therese,  460. 

Thevenot,  535. 

Thiele,  27,  28,  33. 

Thierfelder,  267. 

Thomas,  509. 

Thompson,  218. 

Tigerstedt,  8,  36,  37. 

Tizzoni,  205,  206,  429,  460,  463,  489. 

Tollens,  127,  137,  142. 

Traube,  L.,  31,  39,  152,  474,  488,  493. 

Treutler,  514. 

Trousseau,   112,  126,  244,  261,  334. 

Tschirkoff,  212. 

Turck,  282,  283. 

Turner,  395. 


U 


Umber,  266. 
Uthoff,  241. 


Velich,  208. 
Velsch,  545. 
Verdun,  563. 
Verga,  229,  238. 
Verworn,  52. 
Vessalle,  460. 
Vidal,  245,  261. 
Vieli,  417. 

VlERORDT,    528. 

Virchow,  204,  209,  240,  244,  329,  331,  338, 

344,  347,  370,  377,  423,  425,  431,  432, 

528. 
Vitrac,  536. 
Vogel,  42,  268. 
Vogler,  528. 
v.  Voit,  1,  4,  6,  7,  9,  10,  11,  13,  14,  15,  16, 

18,  19,  20,  21,  22,  23,  33,  41,  44,  45, 

50,  51,  56,  57,  352,  353. 
Volhard,  46. 
v.  Volkmann,  R.,  243,  244,  246,  261,  319, 

531. 
Vulpian,  209. 


W 


Wadd,  163. 

Wagenmann,  535. 

Waldeyer,  231. 

de  Waldheim,  Fischer,  566. 

Wallach,  80. 

Ward,  517. 

Warthin,  369,  383. 

Weichselbaum,  250,  256,  261. 

Weigert,  465. 

Weil,  Emil,  119,  144. 

Weinland,  515,  516. 

Weintraud,  1,  28,  33,  47. 

Wells,  Gideon,  190,  193,  195. 

Wendelstadt,  192. 

Werlhof,  453,  457. 

Westphal,  124,  534,  544. 

Wichmann,  R.,  256. 

Widal,  460. 

Wiedemann,  540. 

Wierus,  390. 

WlERUSZSKIJ,    394. 

Wijnhoff,  506. 

WlKNER,    462. 

Wilks,  370,  387. 
Willan,  470. 
Winogradoff,  511,  512. 

WlNTEKBERG,    542. 


INDEX   OF   AUTHORS 


613 


WlXTERXITZ,   H.,  25. 
WlNZERLING,    536. 
WlTTAN,    479. 

Wohlgemuth.  266. 
Wohlmann,  255,  259,  261. 

WOLPERT,    25. 

Weight,  A.  E.,  292,  296,  398,  399. 
Wucherer,  5(50. 
Wunderlich,  330,  470. 


Yamagiva,  511. 


Z 

Zeder,  548. 
Zeehuisen,  506. 
v.  Zenker,  .">">:;.  554. 
Zenner,  2  18. 

ZlEGLER,    535. 
ZlEMANN,    292. 
V.   ZlEMSSEN,   322,   379. 
Zinn,  so.  81,  ■"><•>:■!.  545. 
Zondek,  445. 

ZUNEER,    507. 

Zuntz,  s.  is.  22,  23,  24,  30,  32,  :;i.  :;.-,. 


INDEX 


Abdominal  cavity,  echinococcus  in,  531. 

lymphadenoids  in,  375. 
Abdominal  lymph-channels,  displaced,  383. 
Abdominal  sympathetic,  disease  of,  111. 
Abortion   causing  thrombophlebitis,   478. 
Abscess  of  liver  in  dysentery,  505. 
Absorption,  increase  of,  by  stasis,  259. 

of  food,  disturbances  of,  43. 

of  food,  insufficient,  G. 
Acanthocephala,  565. 
Acarus,  harvest,  565. 

of  birds,  565. 

transmitted  by  prostitutes,  567. 
Acetone  reaction,  102. 
Acetonuria,  91. 
Achylia,  47. 

gastrica,  313. 
Acid,  idycuronic,  262,  267. 
Acid  poisoning,  diagnosis  and  prognosis  of, 

580. 
Acidosis,  87,  90,  95,  97,  102,  579. 
Acids,  use  of,  in  obesity,  178. 
Acquired  diseases,  414. 
Acromegalia,  1 95,  229. 

autopsy  reports  of,  230. 

benign,  233. 

bony  enlargement  in,  234. 

combination  of,  with  diabetes,  233. 

development  of  jaw  in,  235. 

disproportion  of  bodily  parts  in,  -'•'.<>. 

dural  ion  of,  23  I. 

enlarge at  of  soft  parts  in,  237. 

etiology  of,  230. 

eye  changes  in,  232 

functional   structures   in,   236. 

malignant,  233,  239,  241. 

nervous  phenomena  caused  by,  233. 

pathological  anatomy  of,  237. 

pai bology  of,  23  I. 

photographs  of  cases  of,  231. 


Acromegalia,  symptoms  of,  231. 

therapy  of,  212. 
Addison's  disease,  199. 

aggravation  and  improvement  of,  225. 

atypical  cases  of,  218. 

autopsy  reports  of,  214. 

cardiac  weakness  in,  211. 

cases  of  remission  in,  225. 

changes  of  the  nervous  system  in,  215, 
216. 

clinical  picture  of,  200,  210,  215,  222. 

course  and  duration  of,  210. 

cutaneous  complications  of,  202. 

dependence  of,  upon  tuberculosis,  221. 

deviations  from  type  of,  214. 

diagnosis  of,  222. 

experimental  investigation  of.  206. 
ric  and  intestinal  symptoms  in,  21 1. 

general  cachexia,  a  cause  of,  221. 

general  condition-  in,  203,  221. 

histology  of,  222. 

intestinal  symptoms  in,  218. 

muscular  weakness  in,  200. 

nature  of,   210. 

nervous  and  toxic  theories  of.  221. 

nervous  symptoms  in.  201,  206. 

operative  cure  of.  22 1. 

pathologico-anatomical  lesions  of,  202. 

pigmentation  of  skin  in.  218. 

recognil  ion  of,  222. 

sp<  intaneous  course  of,  226. 

statistics  of.  21  I. 

treatment  of.  223,  224,  228 

urine  in,  212. 

Addison's  disease  with  fluctuating  course, 
Addison's  disease  without  adrenal  affection, 

21  t. 

without  bronzing,  21  I. 
Adenomata,  malignant,  2 
Adipose  tissue,  development  of,  64. 
Adipose  ' issue,  in  anemia.  308 


616 


INDEX 


Adipositas,  151. 

Adolescents,  chlorosis  in,  320,  336. 

obesity  of,  68,  154. 
Adrenal  glands,  tumors  of,  219. 
Adrenal  insufficiency,  223. 
Adrenal    parenchyma,    chemical    investiga- 
tions of,  209. 
Adrenal  tablets,  226. 
Adrenal  therapy,  results  of,  227. 
Adrenals,  absence  of  function  of,  228. 

accessory,  206,  220. 

anatomy  and  physiology  of,  204. 

animal,  implantation  of,  226. 

ascending  disease  of,  220. 

atrophy  of,  202. 

cessation  of  function  of,  199,  222. 

changes  of,  in  Addison's  disease,  203. 

chemistry  of,  222. 

degeneration  of,  214,  223. 

disease  of,  199,  202. 

differing  from  typical  Addison's,  215, 
220. 

extirpation  of,.  205,  206,  219. 

function  of,  203,  207. 

functional  disturbance  of,  218. 

organic  extract  of,  197,  207,  226  (see 
also  Suprarenal). 

inflammation  surrounding,  203. 

internal  secretion  of,  209. 

malignant  tumors  of,  220. 

nature  of,  203. 

necessity  of,  to  life,  205. 

neoplasms  of,  202. 

parenchyma  of,  221. 

physiologic  function  of,  205. 

pigment   in,   209. 

protective  functions  of,  207. 

supplementary,  206. 

unchanged    condition    of,    in    Addison's 
disease,  219. 

use  of,  in  natural  condition,  226. 
Adrenalin  to  arrest  bleeding,  454. 
Adynamia,  200. 
Affections  of  bones  and  joints  in  the  obese, 

69. 
Agaricus  poisoning,  599. 
Aged,  metabolism  of  the,  36. 
Aglycosuria,  93,  95. 

dietetic,  87. 
Air,  fresh,  reduced  consumption  of,  333. 
Albumin,  absorption  of,  in  the  sick,  47. 

accumulation  of,  41. 


Albumin,  circulating,  11,  57. 

dead  and  living,  3. 

decomposition  of,  7,  11,  39. 
in  ankylostomiasis,  563. 

deficiency  and  superfluity  of,  11. 

introduction  of,  11. 

nuclear,  52. 

organic,  16,  43. 

reserve,  16,  41,  57. 

splitting  of,  13. 

superfluous  amounts  of,  12. 

toxogenous  decomposition  of,  39,  40. 
Albumin  and  iron  preparations,  341. 
Albumin  as  a  "working  mass,"   16. 

as  basis  of  metabolic  products,  2. 
Albumin  bodies,  10,  70. 
Albumin  deposition,  15. 
Albumin  in  food,  indispensability  of,  10. 

minimal  amount  of,  74. 
Albumin  in  urine  of  diabetics,  121. 
Albumin  metabolism,  35. 
Albumin  minimum,  10,  13. 

hygienic  and  physiologic,  11. 
Albumin  of  body,  43,  55. 
Albumin  of  the  food,  43,  73. 

action  of,  in  nutrition,  71. 
Albumin  savers,  15,  40. 
Albuminuria,  86. 

in  diabetes,  86. 

in  leukemia,  353. 

in  morbus  maculosus,  475,  498. 

in  purpura,  493. 
Alcohol,  energy  carried  by,  50. 

excess  in,  a  cause  of  diabetes,  119. 

gout  caused  by,  127,  130. 

in  beer,  106. 

premature  indulgence  in,  332. 

use  of,  in  the  cure  of  obesity,  74. 
in  diabetes,  101. 
Alcoholism,  chronic,  591. 
Aleuronat,  70,  167. 
Alkali  tension,  286. 
Alkalies,  salts  of,  poisoning  by,  582. 
Alkalimeter,  286. 
Alkaloids,  poisoning  from,  594. 
Alloxur  bodies,  374. 
Aloin  poisoning,  598. 
Alopecia  in  gout,  143. 
Amanita  phalloides,  600. 
Amebre,  505. 

occurrence  of,  in  various  parts  of  body, 
505,  506. 


INDEX 


617 


Ameboid  movement,  346. 

Amenorrhea  in  myxedema,  185. 

American  Pediatric  Society's  investigation 

of  infantile  scurvy,  393,  401.   185. 
American  remedy  for  gout,  13.5. 
Amido-benzol  poisoning.  592. 
Amphistomum  hominis,  508. 
Amyloid  degeneration,  250. 
Anacidity  of  stomach,  47. 
Anatomical    changes    in    chronic    articular 

rheumatism,  2  18. 
Anematosis,  221. 
Anemia,  304. 

absence  of  nervous  symptoms  in,  328. 

ascarides,  a  cause  of,  5  19. 

blood  changes  in,  301,  306,  328. 

blood  examination  in,  307.  309. 

bothriocephalus,  31 1.  317. 

caused  by  uncinaria,  318. 

change  of  climate  in,  310,  319. 

clinical  symptomatology  of,  308. 

cold  applications  in.  310. 

combination  of,  with  obesity,  156. 
decreased  metabolism  in,  33. 
destruction  of  tissue  in,  39. 
differentiation  of  simple  from  pernicious, 

317. 
excessive,  359. 
fatty  degeneration  of,  308. 

faulty  nutrition  a  cause  of,  306. 

general  metabolism  of,  308. 

neral  treatment  of,  319. 
hemorrhagic  diathesis  in,  308. 
idiopathic,  306. 

infantum  pseudoleukemica,  382. 
jaundice  in,  312. 

leukemia,  caused  by,  352,  357,  367. 
lymphatica,  370. 
lymphaticolienalis,  370. 
montana,  560. 
of  brickmakers,  560. 
pernicious,  17.  305,  31  I.  382. 
post-  malarial,  31 B. 

profound.  203. 

progressive  pernicious,  305,  310,  563. 
cardiac  symptoms  in,  313. 
clinical  picture  of,  312. 
course  of,  -">I7. 
forms  of,  •'•!  I. 
metabolism  in,  •"•! 3. 
poel  mortem  findings  in,  31  I. 
primary,  ■">lo. 


Anemia,    progressive   pernicious,  remission 
in,  317. 
symptoms  of,  311. 
tumor  formation  in,  315. 
secondary  or  symptomatic,  305. 
severe,  357,  358. 
simple,  305. 

cause  of,  305. 
diagnosis  of,  309. 
prognosis  of,  309. 
treatment  of,  309. 
chronic,  381. 
splenic,  326,  381. 
therapy  of,  318. 
variety   of,    indicated   by    blood    changes, 

312. 
well-nourished  appearance  in,  313. 
Anemia  in  Hodgkin's  disease,  373. 
Anemia  from  tape-worm,  523. 
Anemics  with  normal  hemoglobin,  281. 
Angina  pectoris,  141. 
Angina  pectoris  in  diabetes,  85. 
Angioneurosis,  1  Is. 
Anguillula,  development  of,  545. 

intesl  inalis  el  stercoralis,  Bavay,  54  1.  5  15. 
putrefaciens,  54 1. 
Anilin  poisoning,  592. 
Animal  economy.  1. 
Animal  poisons,  598. 

Animal  parasites  of  man.  501. 

Animal  protoplasm,  decomposition  of,  52. 
Animals,  echinococcus  disease  among,  529. 

fattening  of,   153. 

parasites  derived  from.  503. 

Ankle,  >prain  of,  1  10. 

Ankylosis,  250. 
fibrous,  250. 

of  bleeder-,    138. 

Ankylostoma,  501. 

disturbances  caused  by,  50 i. 

duodenale,  561 , 
Ankylostomiasis,  560 

autopsy  findings  ol 

prophylaxis  and  treatment  of, 

symptoms  of,  562. 
Anorexia,  323. 

in  gout,  1  10. 
Anthrax,  57 1 . 

Antitat  cur,-.  72,   100.   170. 

indication  for 
irral ional,  55. 
metabolism  in,  56. 


618 


INDEX 


Antipyrin  poisoning,  594. 
Antirheumatics,  in  gout,  149. 
Antitoxic  action  in  adrenals,  221. 
Anus,  itching  of,  551. 
Aorta,  aneurism  of,  216. 

chlorotica,  329. 

of  hemophiliacs,  431. 
Apepsia.     See  Achylia. 

gastrica,  47. 
Apparatus,  use  of,  in  rheumatism,  259. 
Appetite,  29. 

caprices  of,  60,  323,  428. 

diminished  by  decreased  fluid  intake,  75. 

enormous,  in  diabetes,  113. 
Appetite  in  the  healthy  and  the  sick,  22. 
Appetite  of  the  obese,  157. 
Arabinose,  267. 
Argas  reflexus,  Fabricius,  566. 
Argas,  varieties  of,  566. 
Arnican  poisoning,  598. 
Arnica,  tincture  of,  598. 
Aromatics,  poisoning  by,  592. 
Arsenic,  idiosyncrasy  for,  319. 

in  treatment  of  anemia,  309. 
chlorosis,  343. 
gout,  149. 

Hodgkin 's  disease,  378. 
myxedema,  192. 
pseudo-leukemia,  386. 

poisoning  by,  586. 
Arsenic  atoxyl,  379. 

Arsenious  acid  in  Hodgkin's  disease,  379. 
Artefacts,  356. 
Arteries,  atheromatous  degeneration  of,  157. 

central,  marantic  thrombosis  of,  358. 

compression  of,  for  hemorrhage,  454. 

condition  of,  as  indication  of  age,  81. 

peripheral,  pulsation  of,  322. 

pulsation  of,  in  anemia,  313. 
Arteriosclerosis,  differentiation  of,  from  dia- 
betes, 121. 

in  diabetes,  85. 
Arthritic  gout,  primary,  131. 
Arthritis,  125,  493. 

chronic,  Heberden's  nodes  in,  248. 

deformans,  244,  246. 

gouty,  125. 

hereditary,  253. 

in  hemorrhagic  diseases,  476. 

pauperum,   253. 

urica,  125. 
Arthritisme,  252,  255. 


Arthropathies,  hemophilic,  455. 
Arthropoda,  565. 

Articulation,  sterno-clavicular,  322. 
Ascarides,  causing  suffocation,  550. 

expulsion  of,  by  santonin,  550. 

occurrence  of,  in  various  parts  of  body, 
549,  550. 
Ascaris,  infection  of  children  by,  549. 

lumbricoides,  Linne,  548. 

maritima,  Leuckart,  549. 

mystax,  Zeder,  548. 
Ascites,  nitrogen  balance  after,  43. 

occurrence  of,  in  pseudo-leukemia,  386. 
Asphyxia  arsenicalis,  586. 
Assafetida,  in  diabetes,  122. 
Assimilation,  insufficient,  44. 
Asthenia,  in  Addison's  disease,  210. 
Asthma,   174. 
Athyreoidism,  225. 
Athyreosis  chronica,  188. 
Atomatropin,  601. 
Atoxyl,   386. 

Atrophy  in  a  nursling,  47. 
Atrophy  of  ganglion  cells,  217. 
Atropin,  in  diabetes,  123. 
Atropin  poisoning,  597. 
Auscultatory  phenomena,  536. 
Austrian  marine,  scurvy  in,  412. 
Autointoxication,  199. 
Autopsy  findings  in  Addison's  disease,  203. 
Azoturia,  22. 

B 

Babes,  bacillus  found  by,  394. 
Bachstrom's  theory  of  scurvy,  397. 
Bacillus  anthracis,  461. 

hemorrhagicus  Kolb,  490. 

hemorrhagicus  velenosus,  489. 

of  plague,  571. 

of  typhoid,  571. 

producing  scurvy,  399. 

purpura-,  460,  461,  467. 

pyocyaneus  ß,  461. 
Balanitis  of  prepuce,  551. 
Balantidium  coli,  501. 

minutum,  508. 
Balsam  of  Peru,  for  scabies,  569. 
Banting,  cure  for  corpulence,  70,  72,  73,  74, 

163,  164,  165,  166,  173,  175. 
Banti's  disease,  370,  381. 

clinical  picture  of,  381. 


INDEX 


619 


Banti's  disease,  lienal  and  splenic,  381. 

urine  in,  382. 
Bandage,  rubber,  in  rheumatism,  258. 
Barium,  poisoning  by  combinations  of,  583. 
Barlow's  disease,  396,  485,  486,  487. 

increase  of,  in  Berlin,  486. 
Basedow's  disease,   64,  65,    193.     See  also 

(1  raves'  disease. 
Bath  cure,  101,  148. 

for  gout,  135. 

in  diabetes,  101. 
Baths,  hot,  for  chlorotics,  341. 

mud,  148. 

peat,  148. 

sulphur  mud,  148. 

sun,  of  Celsus,  1  75. 

thermal,  1  18. 

value  of,  in  diabetes,  122. 

with  electric  light,  258. 
Bear's  paw  of  acromegalia,  234. 
Bed-bugs,  transmission  of  parasites  by,  571. 

varieties  of,  572. 
Beer,  as  preventive  of  scurvy,  111. 

consumption  of,  in  Munich,  130. 

effects  of,  in  diabetes,  100. 

use  of,  in  obesity,  170. 
Beer  glycosuria.   79. 

Belles-lettres,  influence  of,  on  girls,  338. 
Benzine,  in  trichinosis,  560. 
Bernard,  Claude,  experiments  of,  L15,  116. 
Bial's  reagent,  263. 

tests  for  pentose,  267. 
Bicycling,  (17.  72. 

in  obesity,  1 76. 
Bidder    and    Schmidt's    investigations    in 
metabolism,   1. 

Bier's  hot   air  t  reatinent.  259. 

Bile,  chemical  composition  of,  345. 

stasis  of,  16. 
Bile-ducts,  dilatation  and  inflammation  of, 

512. 
Bilharzia  hsmatobia,  512. 

pre\ alence  of   in   Urica,  512. 
Biliary  passages,  inflammation  of,  l  in. 
Biogen  molecule,  52. 
Bird  acarus,  565. 

Bites  of  insed  i,  I  reatmenl  of,  575. 
Bitters,  poisoning  l>y.  -Vis. 

BUgar  contained  in.   Uli . 

Biuret  react  ion,  •">! . 
Bladder,  distoma  infection  in,  513. 
echinococci  of,  5 12. 


Bleeder  families,  415,  416,  417. 

Bleeder's  disease,  413.    See  also  Hemophilia. 

joint.  432.  439.  440. 
Bleeders,  marriage  of,  452. 
Blindness,  color,  418. 

night,   419. 

transitory,  32Ö. 
Blood,  abnormal  composition  of,  427. 

abnormal  distribution  of,  281. 

agglutination  of,  290. 

albumin  in,  307,  312. 

alkalinity  of,  276,  286. 

anemic  composition  of,  324,  336. 

bacteriology  of,  290. 

changes    of,    in    progressive    pernicious 
anemia,  31 1. 

chlorotic.  :!_'f>. 

circulation  of,  304. 

coagulability  of,   15  I. 

coloring  matter  of,  325. 

composition  of,  favoring  hemophilia,  422. 
in  purpura,  494. 

condition  of,  in  hemophilia,  424. 
in  purpuric  child,  495. 
in  scurvy,  40S. 

dilution  of,  282. 

diseases  of,   273. 

fixing  methods  of  examination  of,  292. 

flooding  of,  with  sugar,  79. 

fluid  constituent-  of,  327. 

impoverished,  33. 

injection  of,  206. 

inspissation  of,  124. 

insufficient  coagulability  of,  123. 

intensity  of  color  of,  277. 
internal  secretions  in.  33  I. 
leukemic,  composil  ion  of,  344. 
lymph-cell  formation  in,  361. 
methemaglobin  in,  in  poisoning,  583. 
morphological  alteration-,  of,  31 1 .  333. 
pallor  of,  in  chlorosis,  325. 
pathology  of,  •'>  15. 
pigment  originating  in,  213. 
processes  for  staining,  -".••'!.  294. 
protective  bodies  of,  276. 
regeneration  of,  305. 
shadow  corpuscles  in.  195. 
shadow  formation  in,  162. 
solids  of,  307,  312. 
specific  gravity  of,  284,  307,  •'512. 
sped  roscopic  examinal  ion  of, 
the  Beal  of  chlorotic  disease  in, 


620 


INDEX 


Blood,  total  solids  in,  285. 
transfusion  of,  319. 
uric  acid  in,  255. 
Blood  cell  formation,  infectious  disturbance 

of,  362. 
Blood  cells,  323. 
acidophilic,  297. 
anomalies  of,  299. 
circulating,  310. 
eosinophilic,  297. 
mononuclear,  346. 
non-nucleated,  345. 
nucleated,  326. 
oxyphilic,  297. 
red,  counting  of,  325. 

reduction  of,  327. 
varying  size  of,  326. 
Blood  changes  in  Addison's  disease,  212. 
Blood-corpuscles,  281. 

condition  of,  in  chlorosis,  325. 

counting  of,  281,  325. 

normal  numbers  of,  283. 

nucleated,  349. 

percentage  of,  in  anemia,  306. 

pessary  forms  of,  496. 

red,  counting  of,  325. 

condition  of,  in  anemia,  306. 
formation  of,  344. 
reduction  of,  312. 
volume  of,  287. 
white,  283,  307. 

condition  of,  in  leukemia,  360. 
increase  of,  344,  355. 
number  of,  300. 
polymorphia  of,  364. 
Blood  count  in  Addison's  disease,  204. 
Blood-counting,  apparatus  for,  281. 
Blood  examination,  275. 

in  diseases  of  bone-marrow,  275. 
in  malaria,  291. 
in  parasitic  diseases,  275. 
method  of,  276. 
Blood-formation,  anomaly  of,  335. 
embryonal  type  of,  310. 
impairment  of,  356. 
morbidly  active,  344. 
pathological,  365. 
peculiarity  of,  in  anemia,  317. 
Blood-kindred,  intermarriage  between,  421. 
Blood  plaques,  327. 

recognition  of,  293,  299. 
Blood-poisons,  592. 


Blood  preparations  containing  iron,  342. 
Blood-pressure  raised  by  adrenal  therapy, 

207,  209. 
Blood  serum,  agglutination  of,  289. 

dilution  of,  289. 

investigation  of,  285. 

methods  for  testing,  289. 

reduction  of,  327. 

total  solids  in,  327. 
Blood-staining,    by    Chenzinsky's    method, 
295. 

by  Ehrlich's  method,  293,  296. 

universal  method  of,  296. 
Blood  tumors,  437. 
Blood-vessel  glands,  238. 
Blood-vessels,  echinococcus  in,  537,  539. 

rupture  of,  431. 
Blood  volume,  in  hemophiliacs,  425. 
Blushing  of  chlorotics,  325,  335. 
Body,  activity  of,  5. 

composition  of,  11. 
Body-albumin,  7. 
Body  landmarks,  displacement  of,  in  obesity, 

159,  160. 
Body  nitrogen,  increase  of,  57. 
Body-weight  as  a  control  in  experiments,  7. 

increase  of,  59. 
Boerhaave's  cases  of  obesity,  160,  162. 
Bone-marrow,  cell  development  in,  347,  348. 

changes  in,  351. 
in  anemia,  315. 

condition  of,  in  pseudo-leukemia,  371. 

functional  alteration  in,  365. 

insufficient  function  of,  360. 

lymphoid  hyperplasia  of,  355. 

pathological  changes  of,  333. 

red,  345. 

reduced  function  of,  362. 
Bones,  affection  of,  by  gout,  139. 

atrophy  of,  251. 

changes  in,  of  hemophiliacs,  456. 

condition  of,  in  scurvy,  407,  408. 

deformities  of,  in  acromegalia,  232. 

echinococcus  of,  544. 

enlargement  of,  in  acromegalia,  234. 

long,  tumor  in  tract  of,  485. 

sensitiveness  of,  to  pressure,  358. 

X-ray  examination  of,  432. 
Bothriocephalic  anemia,  prognosis  of,  524. 

treatment  of,  318. 
Bothriocephalus  cordatus,  Leuckart,  521. 

cristatus,  Davaine,  521. 


INDEX 


621 


Bothriocephalus  grandis,  Blanchard,  521. 

latus,  Bremser,  520. 
distribution  of,  521. 

Mansoni,  Cobbold,  521. 

passage  of  segments  of,  522. 
Botulism,  601. 
Boys,  chlorosis  of,  320,  330. 

gout  in,  129. 
Brain,  distoma  in,  511. 

eehinococci  of,  534. 

effusions  of  blood  into,  158. 

injury  to,  as  cause  of  diabetes,  115. 
Bread,  casein,  170. 

containing  aleuronat  or  ergon,  168. 

diabetic,  99. 

rye,  in  obesity,  173. 

wheat,  for  the  obese,  168,  169. 
Breithaupl  and  Cetti,  the  fastens,  14. 
Brickmakers,  disease  of,  560. 
Bright's  disease,  lt>7.  168. 
Brisemenl  fore6,  156. 
British    Medical    Association,   Congress   of, 

179. 
Bromin  salts,  poisoning  by,  584. 
Bromism,  58  L 

Bronchial  catarrh  in  trichinosis,  557. 

Bronzing  in  Addison's  disease,  201. 

Bruit  de  diable,  322. 

Bui)«»  disease,  571. 

Buffy  coat.  431. 

Bulimia  in  Addison's  disease,  200. 

Bunge'a  theory  of  Bcurvy,  I L0. 

Burns  under  X-ray  treatment,  369,  381. 

Büschel-form  of  keratitis,  567. 


Cabot's,  researches  in  blood  examination, 

283. 
Cachexia  associated  with  pigmentation  of 
skin.  203. 

from  parasites,  511. 

in  Bodgkin'a  disease,  373. 

myxedematous,  L91 , 

-i  rumipriva,  I  s7.  188. 

thyreopriva,  187,  188. 

tubercular,  221 . 
Cachexie  pachydermique,  179. 
Calculi,  uratic,  i">7. 
Calorimel  ry,  dired .  9. 

in  man,  6. 


Calory  estimations,  of  Rubner,  44. 
Calory  requirement  of  body,  6,  7. 
Calory  supply,  diminution  of,  53. 
Calves,  cramps  in.  128,  136. 
Camphor,  in  diabetes.  122. 
Camphor  poisoning,  59  I 
Cancer,  hepatic,  oil. 
Cane-sugar,  78. 
Cantani's  obesity  cure,  165. 
Capillaries,  rupture  of,  433. 
Carbohydrates,  absorption  of,  48. 

allowance  of,  in  diabetes,  98. 
in  the  diet,  7  1. 

in  feces,  estimation  of,  amount  of,   15. 

percentage  of,  in  beer,  106. 
in  food,  tal.les  of,  10  I. 
in  wines  and  spirits,  106. 

tolerance  of,  88. 

value  of,  as  albumin  savers,  40. 
Carbolic  acid  poisoning,  593. 
( 'ail >on  balance,  7. 
Carbon  bisulphid,  586. 
Carbonic  acid,  excretion  of.  S. 
Carbonic  acid  poisoning,  590. 

chronic,  591 . 
Carcinoma,  colloid,  512. 

from  parasitic  infection,  513. 
Carlsbad,  treatment  at,  in  diabetes,  101. 
Casein,  70,  169. 
I  lastor  oil,  in  trichinosis,  559. 

Castration,  a-  a  cause  of  obesity,   1Ö1. 

Cataphoresis,  125. 

Catarrh,  intestinal,  due  to  coccidia,  our,. 

tendency  to.   in  obesity,    1">7. 

( laterpillars,  toxic  effect  of,  575. 

Cattle,   mortality  among,   from  echinocoo- 

cus,  533. 
Cautery,  to  control  hemorrhage,  154. 
Cell  accumulations,  lymphadenoid, 
( 'ell.  protoplasm  of,  3. 

desl  rucl  ion  ol 
( 'ells,  chemical  activity  of,  3. 

decomposition  in,  3. 

dwarf.  356. 

grow  t  h  energy  of.  :,~ . 

katabolic  act  ivity  of.  61. 

nuclei  of.  disease  of.  [31. 

parenchyma,  20 1. 

regeneral  ive  energy  of.  57. 
Cerebral  affections,  due  to  gout,  1  12. 
Cerebral  diseases,  polyuria  in.  115. 
Cerebral  disturbances  in  myxedema.  184. 


G22 


INDEX 


Cervical  ganglia,  neuritic  disease  in,  216. 
Cestodes,  514. 
Cesto-embolism,  539. 
Cetti  and  Breithaupt,  the  fasters,  14,  32. 
Chambers's  cure  of  corpulence,  163. 
Champagne  as  cause  of  gouty  attack,  135. 
Charcoal  in  calorimetric  investigations,  6. 
Charcot  on  rheumatism.  244. 
Charcot-Leyden  crystals,  350,  563. 
Cheese,  in  diet  of  diabetes,  100. 
Chemical  analysis,  in  case  of  poisoning,  581. 
Chemical  curative  agents,  197. 
Chemical  processes  as  source  of  heat,  2. 
Chemotactic  stimulus,  344. 
Chemotaxis,  365. 

negative  and  positive,  302. 
Cherry  cure,  147. 
Chicken  cholera,  571. 
Children,  metabolism  of,  36. 
Chin,  double,  159. 
China,  organotherapy  in,  196. 
Chiragra,  125. 

Chlorin  combinations,  poisoning  by,  583. 
Chloroform  poisoning,  584. 
Chlorosis,  305,  320. 

anatomical  foundation  of,  330. 

appetite  in,  caprices  of,  323. 

blood  changes  in,  325,  327,  334. 

blood  examination  in,  325,  328,  336. 

body  temperature  in,  323. 

cardiac  murmurs  in,  321. 

cardiac  palpitation  in,  322. 

causes  of,  333. 

changes  of  skin  in,  320. 

combination  of,  with  obesity,  156. 

complications  of,  329. 

course  of,  337. 

derangement  of  nervous  system  a  cause 
of,  335,  336. 

development  of,  339. 

diagnosis  of,  328,  336. 

diet  in.  311. 

digestive  symptoms  in,  323. 

diseased  blood  as  a  cause  of,  334. 

Egyptian,  560. 

extreme  pallor  in,  336. 

forms  of,  337. 

frequency  of,  in  cities,  331,  333. 

genesis  of,  333. 

gigantea,  154. 

habitual,  330. 

hereditary,  339. 


Chlorosis,  independent  symptoms  of,  324. 

latent,  329. 

metabolism  in,  33. 

mode  of  life  favoring,  339. 

murmurs  in,  321. 

nervous  disturbances  of,  324,  325. 

no  specific  treatment  for,  340. 

occurrence  of,  among  servant  girls,  332. 
in  boys,  320,  330. 
in  fat  people,  320. 
in  men,  329. 
in  time  of  Hippocrates,  320. 

pathological  anatomy  of,  329. 

persistent,  330. 

predisposing  causes  of,  331. 

prognosis  of,  329. 

prophylaxis  of,  343. 

rapidity  of  pulse  in,  322. 

relapses  of,  330. 

relation  of,  to  sex,  330. 

respiratory  apparatus  in,  323. 

sexual  functions  in,  323. 

symptomatology  of,  328. 

tight  lacing  a  cause  of,  332. 

treatment  of,  339. 
by  suggestion,  342. 

tropical,  560. 

vagaries  of  appetite  in,  323. 
Cholelithiasis,  140. 
Cholera    Asiatica,    simulated    by    arsenical 

poisoning,  586. 
Choleraic  symptoms,  in  trichinosis,  556. 
Chorea,  thyreoid  therapy  in,  195. 
Chronic  articular  rheumatism,  243. 
Chyle  tracts,  48. 
Cimex,  varieties  of,  572. 
Circulatory  apparatus,  changes  in,  329. 

condition  of,  in  chlorosis,  321. 

echinococcus  in,  538. 
Circulatory  disturbances  as  result  of  obesity, 

69. 
Circumcision,  of  hemophiliacs,  434,  452. 
Cirrhosis,  hepatic,  43,  382. 

hypertrophic  hepatic,  141. 

of  liver  from  parasitic  changes.  512. 
Claudicatio  intermittens,  85. 
Climacterium,  use  of  oöphorin  in,  197. 
Climate,  influence  of,  in  producing  scurvy, 

397. 
Clothing,  use  of,  in  common,  550. 
Club  finger  tips,  256. 
Club-foot,  as  sequence  of  scurvy,  409. 


INDEX 


G23 


Coal  gas  poisoning,  79. 
Cocain  poisoning,  597. 
Cocainism,  597. 
Coccidium,  bigernimum,  506. 

oviforme,  506. 

perforans,  506. 
Colchicum  in  gout,  149. 
Cold  and  heat,  effect  of,  in  metabolism,  25. 
Cold,  extreme,  a  cause  of  diabetes  insipidus, 
119. 

use  of,  in  diabetes,  122. 
Colic,  lead,  587. 

renal,  451. 
Collapse,  cardiac,  596. 

treatment  of,  497. 
Colloid  masses,  excretion  of,  204. 
Color-blindness,  418. 
Color-index,  283. 
Coma,  acid,  92. 

diabetic,  80,  91,  102. 

fatal,  in  anemia,  319. 

in  purpura,  483. 

opium,  596. 
Combustion,  a  source  of  energy  and  heat,  2. 

increase  and  decrease  of,  26. 
Compensation,  process  of,  88. 
Comptodact  v  1  i i  ■ ,  '_'.V> . 
Congress,  British  Medical  Association,  179. 

Forth  French,  for  Urology,  1889,  lis. 

International  .Medical,  at  Pari-,  126,  127. 
Congress  of  Interna]  Medicine,  lss.j.  50. 
Connective  tissue,  3  18. 

changes  of,  in  acromegalia,  -'-',7. 
Connective  tissue  hyperplasia,  237,  238. 
Constipation  in  chlorosis,  323. 

in  gout,  1  in.  1  is. 

in  scurvy,  1 13. 

obstinate,  in  the  obese;  157. 

stubborn,  172. 
Consumption,  occurrence  of ,  in  small  eater-, 

63. 
< lonl racturee  of  fingers  and  toes,  251 . 
Convalescence,  abundance  of  food  in,  in. 

in  morbus  maculosus,  197. 
Copaiba,  balsam  of,  poisoning  by,  594. 
( ioprostasis  in  chlorosis,  3 10. 
Corium,  pigmentation  in  deep  layers  of ,  213. 
Cornutin  poisoning,  598. 

Coronary  artery,  calcification  of,  269 

Corpulence,  151.    See  also  Obesity. 

\\  add'-  \  iews  '>n.  163. 
Corrosive  Bublimate,  tolerance  of,  589. 


Corrosive  sublimate  poisoning,  symptoms  of, 

589. 
Corsets,  injurious  effects  of,  332. 
Country  life  for  chlorotics,  340. 
Cramps  in  legs,  139. 
Cream,  in  diet  of  diabetics,  100. 
Creeping  disease.  57  L 
Cremation  of  infected  meat,  533. 
( Iretinism,  30,  187. 

endemic,  188,  189. 

sporadic,  187,  188. 
Cretinoid  state  in  women,  180. 
Crick  in  the  back,  139. 
Crusades,  scurvy  during,  390. 
Crystallose,  109. 
Cure,  Nature-healing,  60. 

Oertel,  174. 

of  obesity,  177. 
Cures,  dietetic  5  1. 

mineral  water,  in  diabetes,  92,  101. 

weakening,  67. 
Cyanosis  in  blood  poison,  592. 
Cyclops  serrulatus.  bischer.  .">_'<). 

Cyprinotus  mcongruens,  519. 
( 'ystericus  bovis,  1  15. 
cellulosae,  501 .  515. 
Cystoid  echinococcus,  528. 


D 


Daltonism,  hereditary,  1 l">.  1  is. 
Deafness  from  lymphatic  nodules.  352. 
Debove's  treatmenl  of  obesity.  161. 
I  decomposition,  alterations  of,  1. 
nuclein,  52. 

Of  food,  fi. 

Deformity,     in     chronic     articular     rheu- 
matism, 2  Hi. 
of  bones  in  arthritis,  256. 
I  Regeneration,  amyloid,  17. 
granular,  326. 
hyaline,  vascular,  166. 
phenomena  of,  326. 
Deglutition,  difficult,  373. 
I »elirium  tremens,  591. 
I temodex  folliculorum,  Simon. 
Dentition,  a  critical  period  in  hemophiliacs, 
134. 
ion,  hypochondriac,  1  I-'- 

par<>\\  -m-  of,    143. 

I  »extra  rotary  pentose,  267. 


624 


INDEX 


Dextrose,  77. 
Dextrosuria,  77. 
Diabete  azoturique,  113. 
Diabetes,  actual  cure  of,  82. 
arteriosclerotic,  84. 
arthriticus,  144. 
cerebral  causes  of,  122. 
chronic,  81. 

coexistent  with  acromegalia,  233. 
combination  of,  with  pentosuria,  268. 
decipiens,  144. 
diet  in,  33. 

disease  of  the  brain  a  cause  of,  114. 
drug  treatment  of,  122. 
gastric  disturbances  in,  102. 
hysterical,  117. 
increased  appetite  in,  113. 
insipidus,  110. 

clinical  picture  of,  110. 

constitutional  condition  in,  120. 

diagnosis  of,  121. 

etiologic  therapy  of,  122. 

etiology  of,  112. 

hereditary  form  of,  119. 

idiopathic  form  of,  1 18. 

infectious  diseases,  followed  by,  119. 

low  temperature  in,  114. 

normal,  117. 

organic  disease   of  brain,  a  cause  of, 
111. 

over-nutrition  in,  64. 

prognosis  of,  120. 

psychical  treatment  of,  122. 

special  varieties  of,  115. 

symptoms  and  course  of,  112. 

typical  cases  of,  120. 
mellitus,  77,  83,  167. 

after  scarlatina,  80. 

combination  of,  with  gout,  130. 

hereditary,  82. 

metabolism  in,  32. 

mild  and  severe  forms  of,  83. 

occurrence  of,  in  the  young,  81. 

over-nutrition  in,  64. 

practical  therapy  of,  92. 

regulated  diet  for,  96. 

theoretic  treatment  of,  87. 

valuable  foods  in,  89. 

various  forms  of,  83. 
mild  and  severe,  83. 
nutrition  in,  113. 
occurrence  of,  in  a  chemist,  80. 


Diabetes,  occurrence  of,  in  the  aged  and  in 
the  young,  80,  81. 
in  the  obese,  83. 

organic,  81. 

pancreatic,  81. 

pure,  84. 

quantitative  diet  in,  98, 

relations  of,  to  gout,  144. 

saccharin,  115. 

sugar  excretion  in,  52. 

tables  of  foods  in,  103. 

thirst  in,  113. 

treatment  of,  87,  101. 

typical  cases  of,  94. 
Diaceturia,  91. 
Diaphragm,  inactivity  of,  557. 

rupture  into,  538. 
Diaptomus  spinosus,  Daday,  520. 
Diarrhea,  fatty,  47. 

in  leukemia,  369. 

in  scurvy,  408. 
Diatheses,  hemorrhagic,  388. 
Diathesis,  gouty,  130. 

hemorrhagic,  in  anemia,  308. 

oxalate,  449. 

uric  acid,  126. 
Didymin,  197. 
Diet,  amylaceous,  80. 

antifat,  grades  of,  72. 

calculation  of  nutrition  and  calory  value 
of,  107. 

effect  of,  in  metabolism,  44. 

employment  of,  in  chlorotics,  340,  341. 
for  the  obese,  167. 
in  diabetes,  87,  96,  122. 
in  leukemia,  369. 

maintenance,  of  the  sick,  37. 

mixed,  80. 

nutrition  and  calory  value  of,  107. 

preventive  of  scurvy,  411,  412. 

quantitative  regulation  of,  96. 

researches  in,  48. 

schemes,  adherence  to,  76. 

tests  in,  48. 

vegetable,  61,  147. 
Diet-tables  of  Chambers,  163. 
Dietary  for  diabetics,  108. 

of  Banting,  72,  74. 

of  Chambers,  163. 

of  Dapper,  73. 

of  Ebstein,  72,  74. 

of  Harvey,  72. 


INDEX 


625 


Dietary  of  Hirschfeld,  74. 

of  Kisch,  74. 

of  Oertel,  72,  74. 

of  v.  Xoorden,  74. 
Dietetic  cures,  54,  69. 
Dietotherapy,  2,  39. 

dangers  of,  102. 
Digestion,   condition  of,   in   Hodgkin 's  dis- 
ease, 381. 

impaired  by  tape-worm,  522. 

physiology  of,  1. 

vicarious  intestinal,  47. 
Digestive  apparatus,   disorders  of,   in   dia- 
betes, 114. 
Digestive  canal,  catarrh  of,  140. 

disturbances    of,    in    Addison's    disease, 
200. 
Digestive  organs  in  anemia.  313. 
Digestive  tract,  anemic  changes  in.  315. 
Digitalis  and   its  glucocides,  poisoning  by, 

597. 
Digitalis  infusion,  decomposition  of,  597. 
Dioptrics,  419. 

Dioxybenzole  poisoning,  593. 
Diplobacilli,  190. 
Distoma,  509,  510. 

fatal  disease  caused  by,  512. 

occurrence  of,  in  China,  India,  and  Japan, 
51 1 . 
Distomatosis,  510. 
Distomum  felineum,  Rivolta,  511. 

haematobium,   Bilharz,  512. 

hepaticum,  Linne",  509. 

pulmonale,  Baelz,  1883,  510. 

mbiricum,  Winogradoff,  511. 

spathulatum,  Leuckart,  511. 

\\  estermanni,  510. 
Dog,  as  transmitter  of  echinococci,  ~>'-). 
Dog  tape-worm,  ">:;i . 

Drinking-water   a-    disseminator   <>f   para- 
sites, 503. 
Dropsy,  oily,   151. 
I  (rugs,  product  ion  of  hysterical  polyuria  by, 

I  is. 
I hipuyi reu'-  contracture,  I  15. 
Dwarf,  acromegalic  skeleton  of,  231. 
Dwarfs,  prehistoric,  229. 
Dysentery,  distoma  found  in  cases  <>f.  51 1. 

intercurrent,  with  scurvy,  108 
I  dyspepsia,  intestinal,  I  10. 

nervous,  no. 

I  dyspnea,  352. 

41 


E 

Ear,  gouty  processes  in,  143. 

gouty  tophi  in,  135. 
Earth,  diseases  caused  by  working  in,  562. 
Ecchondroses  of  rheumatism,  246,  248. 
Ecchymoses   of    purpura,    459,    470,    484, 

488. 
Echinococci,  autosemination  of,  531. 

of  various  organs,  534. 
Echinococcus,  501 . 

areas  infected  by,  529. 

Cysticercus,  529. 

cysts  of,  527,  532. 

expectoration  of  membrane  of,  538. 

multilocular,  534. 

multilocularis,  528. 

multiplex,  531. 

occurrence  of,  in  bones,  529. 
in  female  genital  organs,  543. 
in  oral  cavity,  535. 

prevalence  of,  among  animals,  526. 

prevalence  of  infection  of,  529. 

propagation  of.  527. 

pulmonary.  538. 

renal,  541. 

toxicity  of  fluid  of,  531. 

transmission  of.  by  «lo<_r.  529. 
tumors  of,   528. 
EchinOCOCCUS   disease,    52**>. 

course  and  temperature  in,  540. 

prognosis  of.  .">:;::.  540. 

prophylaxis  of.  .">.;:; 

symptoms  of.  532. 

treatment  of.  533. 

unilocular.  531 .  539, 

with  duration  of  thirty-five  years,  530. 
Echinococcus  sac,  an  impediment  at  birth, 

543. 
Echinorhyncus  gigas,  Goese,  501,  565. 
Ectoparasites,  501 .  565. 
Edema   in   trichinosis,  557. 

Edema    of   face.    .",  1  1  . 

Effusion,  hemorrhagic,  192. 
in  scurvy,  WO, 

into   knee-joint.    155. 

Effusions  in  L'out ,  134. 
!  m  diel  of  diabetics,  100,  108. 

I  Ihrlicfa  '  \  e  pit  ce,  301. 
Ehrlich-Pinkus  formula.  376. 
Ehrlich'«    method    of   staining,    298,    294, 
296. 


626 


INDEX 


Ehrlich's  investigations  of  the  blood,  345, 

351. 
Electricity  to  spleen,  386. 
Electricity,  use  of,  in  diabetes,  123. 
Elephantiasis,  swellings  resembling,  548. 
Emaciation,  cure  of,  161. 

in  diabetes  insipidus,  120. 

in  rheumatism,  250. 

significance  of,  38,  39. 
Emboli,  from  echinococcus  cysts,  537. 

in  trichinosis,  557. 
Embonpoint,  153,  155. 
Emphysema,  pulmonary,   142. 
Endocardium  involved  in  rheumatism,  251. 
Enemata  of  benzine,  560. 
Energy,  law  of  conservation  of,  2. 

loss  of,  43,  44. 

transferrence  of,  3,  11. 

metabolism  of,  5. 
Energy  requirement  of  body,  11. 

of  the  healthy,  9. 
English  navy,  absence  of  scurvy  in,  411. 
Enlargement,  in  acromegalia,  230. 

glandular  and  multiple,  375. 
Enteric  fever  in  chlorotics,  339. 
Entoparasites,  501. 
Entozoa,  501. 
Enuresis  nocturna,  119. 
Enzymes,  action  of,  13. 
Eosinophiles,  347,  355. 

in  trichinosis,  557. 
Eosinophilic  leukocytosis,  365. 
Epidemics  of  trichinosis,  553. 

of  scurvy,  390,  391,392. 
Epididymis,  echinococci  of,  544. 
Epilepsy,  116. 

from  tenia  solium,  504. 
Epinephrin,  210. 

Epinephrectomy  in  animals,  206. 
Episcleritis,  252. 

Epistaxis,  occurrence   of,  in   hemophiliacs, 
454. 

treatment  of,  497. 
Epizoa,  501. 

Equilibrium,  nitrogenous,  10. 
Ergon  in  bread  for  the  obese,  167. 
Ergot,  use  of,  in  hemorrhages,  454. 
Ergot  poisoning,  598. 

chronic,  599. 
Ergotin,  in  diabetes,  123. 
Ergotism,  convulsive,  599. 

gangrenous,  599. 


Eruption,  itching,  544. 
Erythema,  nodosum,  473,  477. 
Erythroblasts,  300. 

in  anemia,  311. 
Erythrocytes,  307,  344. 

decrease  of,  349. 

increased  formation  of,  283. 

morphological  changes  in,  306. 

normal  proportions  of,  345. 

recurrence  of,  in  chlorotic  blood,  326. 

stippling  of,  292,  300,  312. 
Erythrosclerotin,  599. 
Eschars,  from  acid  poisons,  580. 
Esophagus,  ascarides-in,  550. 
Ethyl  alcohol,  poisoning  by,  591. 
Eucalyptus,  in  pseudo-leukemia,  386. 
Eucasin,  48. 

Eustrongylus  gigas,  Rudolphi,  560. 
Excretion  by  skin,  stimulation  of,  123. 
Excretions,  estimation  of,  6. 
Exercise,  bodily,  during  antifat  cures,  56. 

muscular,  in  diabetes,  92. 
in  obesity,  175,  176. 
in  production  of  flesh,  58. 

passive,  177. 
Exercises,  free,  of  German  turners,  176. 
Exophthalmic  goiter,  64,  66,  193. 
Exophthalmos  in  acromegalia,  233. 
Expired  air,  estimation  of,  6. 
Extremities,  neuralgia  of,  314. 

size  of,  in  acromegalia,  230. 
Eye,  affections  of,  hi  rheumatism,  252. 

changes  of,  in  acromegalia,  232. 

Cysticercus  in,  524. 

disease  of,  from  acarus,  569. 
from  caterpillars,  575. 

specks  before,  324. 
Eye-ball,  echinococcus  of,  535. 
Eye-ground  in  leukemia,  352. 
Eyrich's  picture  of  purpura,  484. 


F 


Face,  cyanosis  of,  373. 

edema  of,  373. 
Faradization,  66. 
Fasters,  professional,  14. 
Fasting  values,  9. 
Fat,  combustion  of,  75. 

danger  of,  in  various  diseases,  55. 

development  of,  in  prime  of  life,  55. 


INDEX 


621 


Fat,  divisibility  of,  12. 

estimation  of,  in  feces,  45. 

formation  of,  12,  18,  21,  34. 
excessive,  151,  159. 

increase  of,  55. 

losses  and  accumulations  of,  58. 

mal-a.ssimilation  of,  46. 

nausea  caused  by,  167. 

necessity  of,  as  a  food,  166. 

repugnance  to,  40. 

satiety  caused  by,  167. 

significance  of,  54. 

splitting  of,  46. 

sugar  formation  from,  52. 

tables  of,  in  various  foods,  103. 

place  of,  in  diet,  21,  74. 
of  the  diabetic,  89. 

value  of,  in  diabetes,  100. 
in  various  diseases,  55. 
Fat  of  normal  children,  153. 
Fat  absorption,  decrease  of,  46. 
Fat-albumin  diet,  175. 
Fat   bodies,  poisoning  by,  591. 
Fat  marrow  changes  in  pernicious  anemia, 

316. 
Fat  metabolism,  7.". 
Pat-milk,  Gartner's,  486. 

bats,   neutral,  46. 

Fatigue,  sensation  of,  in  anemia.  308. 

Fattening  of  animals,  153. 

fatty  degeneration  in  progressive  pernicious 

anemia,  315. 
Features,  change  of,  in  myxedema,  184. 
Feces,  albumin  losses  in,  47. 

analysis  of,   15. 

calory  value  of,  4 1. 

elementary  analysis  of,  4. 

estimation  of,  6. 

fatty  acids  in,  16. 

microscopic  examination  of,  522 

parasite-  in.  .".1)7. 
Feeding  forced.    Hi,    19,    10.   ">ii. 
Female  breast  in  obesity,  151. 
Females,  hemophilia  occurring  in,   in. 
Fermentation  test ,  262,  26 l. 

l'ei  rat  in,    342. 

Ferrum  carbonicum,  -ill. 
Ferrum  chloratum,  3  I  1  . 
Ferrum  citricum,  341. 
Ferrum  oxydatum,  341. 
Ferrum  Besquichloratum,  341. 

Ferrum   sulphuricum,   •'■  1 1 


Fever,  chronic  relapsing,  375. 

destruction  of  tissue  in,  39. 

gastric,  80. 

intermittent.   I'.il. 

recurring,  glandular,  375. 

relapsing,  pre-natal,  transmission  of,  429. 

with  glandular  enlargement,  376. 
Filaria  Bancrofti,  Cobbold,  540. 

embryos,  ö  17. 

loa  Guyot,  546. 

Magathsesi,  547. 

medinensis  Velsch,  545. 

varieties  of,  540. 
Fingers,  gout  in,  138. 

nodosities  of,  255. 
Finland,  hemophilia  in,  451. 
Fischer's  test,  77. 
Fish  in  dialietes,  108. 
Fish,  raw,  parasitic  infection  from,  512. 
Fish  poisoning,  000. 
Fixation,  niethylie  alcohol,  293. 
Flagellates.  .">07. 

Flat-foot  occurring  in  the  gouty,  144,  158. 
Flat-worms,  508. 
Fleischl's  hemometer,  277,  278. 
Flesh,  increase  of,  55. 
Flesh  production  by  stock  raisers,  19. 
Fluid  in  blood,  increase  of,  311. 
Fluids,  digestive,  in  metabolism,  4. 

intake  of,  limited  in  diabetes,  124. 

in  obesity,   171. 

simultaneous   intake  of,  with  solid  food, 
75. 
Fly.  a-  carrier  of  infection.  07  1 . 
Fly   larva'.  .".01,   573. 

in  remote  parts  of  body,  .".7  I. 

Follicles,  destruction  of,  186. 

Food,  albuminous,  reduction  of.  97. 

assimilation  of,  i">. 

changes  in,  ill  effects  of,  333. 

consumption  of,  in  1 1 »* -  healthy,  4 

in  tubercular  il 
contamiiiatioii   of,   by   Hi«-,   .".7."). 

decomposition  of.  :>.  I'.i. 
diminished  consumption  of,  82. 
energy  value  of,  :?7. 
faulty  absorption  of.  1 1. 

h,  a-  pre\ entive  of  scurvy,  185. 
indigestible,  craving  for 
intake  of.  influence  of,  23. 
Iimitat ion  of,  in  obesitj .  1  5 I- 

nature    ami    .(iiaiility    of,    21. 


628 


INDEX 


Food,  necessity  of,  for  maintenance,  59. 

oxidation  of,  3. 

parasites  disseminated  by,  511. 

passage  of  tape-worm  caused  by,  522. 

repugnance  for,  323. 

source  of  energy  in,  2. 

sudden  withdrawal  of,  31. 

unclean,  as  disseminator  of  parasites,  503. 

uniform  limitation  of,   174. 
Food  molecule,  as  containing  nitrogen,  51. 
Food  products,  disintegration  of,  2. 

divisibility  of,   12. 

plastic,  2. 

respiratory,  2. 
Food  requirement  of  the  sick,  21. 
Food  surplus,  61. 
Food  values,  compilative  table  of.  14. 

standard,  8. 
Foods,  kinds  of,  for  the  obese,  167. 

percentage  of  fat  in,  103. 

sugar-producing,  89. 
Foot,  gout  in,   125. 
Force,  in  living  organism,  2. 
Force,  interchange  of,  22,  37. 

permutation  of,  2. 
Forced  feeding,  a  cause  of  cardiac  weak- 
ness, 65. 

in  hysteria  and  neurasthenia,  65,  66. 

in  production  of  flesh,  58. 

indications  for,  62. 

technic  of,  70. 
Fowler's  solution  in  Addison's  disease,  224. 

in  morbus  maculosus,  497. 
Fractures,  treatment  of,  by  thyreoid  gland, 

195. 
Freiburg,  prevalence  of  goiter  in,  190. 
Friction  as  source  of  heat,  2. 

in  chlorosis,  340. 
Frontal  sinus,  echinococcus  in,  535. 
Fruits,  108. 

carbohydrate   contents  of,    105. 

dried,  in  diabetes,  99. 

in  diabetes,  99. 

pentosan  in,  268. 


G 

Gadfly  boil,  573. 
Gaertner's  hemophotograph,  279. 
Galactose,  267. 

Ganglia,   semilunar,   inflammation  and  de- 
generation of,  216. 


Gangrene,  of  extremity,  from  ergotism,  599. 
Garrod's  views  of  scurvy,  398,  410. 
Gases,  interchange  of,  30,  36,  308. 

interchange  of,  in  obesity,  154. 
respiratory,  8. 

poisoning  by,  590. 
Gastric  chemism,  disturbance  of,  47. 
Gastric  contents,  examination  of,  323,  340. 
Gastric  dyspepsia  in  gout,  140. 
Gastric  hunger,  60. 

Gastric  juice,  action  of,  on  echinococci,  526. 
Gastrophilus  larva,  574. 
Gastroptosis,  323,  333. 
Gelatin  to  control  hemorrhage,  454. 
Genital  organs,  echinococcus  in,  543. 

examination  of,  337. 

hypoplastic  changes  in,  330. 

implication  of,  in  acromegalia,  238. 
German  marine,  scurvy  in,  412. 
Germany,  parasitic  disease  in,  529. 
Ghida,  125. 

Giant  growth,  195,  230. 
Giant  skull,  pathologic,  229. 
Giants,  prehistoric,  229. 
Gicht.     See  Gout. 
Gigantism,  234,  237. 
Gigantoblasts,  300. 
Gigantocytes,  299,  300. 
Gingivitis,  bacillus  causing,  394. 
Girls,  neuroses  appearing  in,  336. 
Glands,  enlargement  of,  371. 

extirpation  of,  380. 

intestinal  atrophy  of,  47. 

pain  in,  376. 

tuberculosis  of,  375,  376. 
Glandular  disease  caused  by  poison  in  blood, 
378. 

predisposition  to,  378. 
Glandular  organs,  in  scurvy,  400. 
Glaucoma  in  gout,  143. 
Gliomata,  239. 
Glucose,  77. 

Glycogen  deposit,  12,  16. 
Glycogenic  area  of  brain,  114. 
Glycogenic  center,  111. 
Glycosuria,  77. 

alimentary,  77,  78,  79. 
in  gout,  144. 

combination  of,  with  pentosuria,  269. 

diabetic,  87. 

e  saccharo,  79. 

experimental,  79. 


INDEX 


629 


Glycosuria,  nature  of  processes  in,  78. 

physiologic,  77. 

spontaneous,  79,  81. 

transitory,  81. 
Glycosuria  in  morphin  poisoning,  596. 
Gnathostoma  siamen.se,  Levinsen,  560. 
Goiter,  occurrence  of,  in  infants,  190. 

massive,   238. 

parenchymatous,    192. 
( lonagra,  125. 
Gonorrhea.  256.  478. 

gouty,  142. 
Gordius,  varieties  of,  565. 
Gout,   125. 

annual  attack  of.   139. 

cachectic  stage  of,   149. 

cancer,  caused  by,  143. 

causes  of,  126,  127. 

cerebral  affections  in,    1  12. 

clinical  cases  of,  128,  L3 1. 

clinical  history  of.  126. 

combined  with  hematuria,  451. 

condition  of  heart  in.  141 . 

confounding  of,  with  rheumatism,  243. 

course  of.    1  IÖ. 

curative   resorts  for,    1  IV 

decreased  metabolism  in.  :'<■'<. 

diagnosis  of,  1  MS,  L50. 

diel   in,   147. 

edema  in,  134. 

exemption  of  women  from.  1  17. 

faulty  action  of  kidney  a  cause  of.    128. 

fever   in.    134. 

foci  of.   133. 

Garrod's  views  of.  136,  243. 
Heberden's  nodes  in.  2  is. 
hereditary,  128,  I  n. 

intermediate  symptoms  "I.    133,    L39. 

'•internal,"    I  IÖ. 

larval,  I  -J.  I  19. 

latent,  132. 

location  of,  in  extremities,  131,  I  15. 

in  right  toe.   128. 
lymphangitis  in.  1  13. 

materia  peCCaUS  in.    132. 

metabolism  in,  12. 

occurrence  of,  in  adolescents,  129. 

in  ancient    I  imes,   126. 

in  England,  130,  131. 

in  Munich.    130. 

in  ii|i|>er  and  lower  (lasses,  130. 

pain  in,  13 1 


Gout,  paralysis  in,  143. 

paroxysms  of,  136. 

pathogenesis  of,  126. 

predisposition  to,  139. 

premonitions  of,  133,  139. 

primary  arthritic.  1_>7,  138,  140. 
treatment  of,  146. 

prognosis  of,  145,  150. 

prophylaxis  of,  1  17. 

relation  of,  to  chronic  arthritis,  255. 

respiratory  conditions  in,  142. 

retrocedont,  132. 

skin  affections  in,  143. 

specific  treatment  of,  1  is. 

Sydenham's  description  of,  126. 

symptomatology  of,  132,  133,  130. 

t reatmenl  of,  146,  lis.  150. 

by  "patience  and  cotton,"   1  19. 

typical  attack  of,  131,  133. 

visceral,  140. 
Gowers's  hemoglobinometer,  277.  27'J. 
Gram-Weigerl  process,  490. 
Grandidier's  views  of  hemophilia,  415,  452. 
Granular  cells  of  epithelium,  239. 
I  crapes  in  diabetes,  <J9. 
Grape  cure.  1  is. 
Grape-sugar,  12.  264,  270. 

in  the  urine.  77,  78,  262. 

Grasshopper  plague  in  Russia,  :!'.»7. 
(irave>  disease,  28,  29,  38,  70,  193. 

forced  feeding  in,  65. 
('■row th.  excessive,  in  acromegalia,  230 
Gruber-Widal  reaction.  289. 
<  lull,  sir  Win.,  on  myxedema,  17'.» 
Gummata  of  akin  in  diabetes,  121. 

(  rums,  disease  of,    1 13. 
fetor  of.    192. 

gangrene  of,  id:?. 

in  purpura,    159,    170. 

lead  line  ..f.  588,  590. 

scorbutic,    Isö. 

spongy,  39  1. 

the  seal  of  BCUn  ,v.   102. 

( lymnastics,  67,  176. 
in  obesity  72 

II 

Hair  in  acromegalia,  237. 
m  scun  y .  105. 

IlallerS  acid.    197 

in  hemophilia,  i"':>. 


630 


INDEX 


Hanimerschlag's  method  for  testing  specific 

gravity  of  the  blood,  284. 
Hardening  processes,  257. 
Harvey's  cure  of  obesity,  70,  72,  163,  165. 
Hayem's  solution,  281. 
Head,  weight  of,  in  acromegalia,  235. 
Health,  calory  requirement  in,  35. 

consumption  of  food  in,  4. 

energy-value  of  food  in,  45. 
Health  resorts,  advantages  of,  339. 

of  Europe,  343. 
Heart  and  vascular  system  in  gout,  141. 
Heart,  defective  development  of,  329,  331. 

dilatation  of,  158. 
in  chlorosis,  322. 

failure  of,  75. 

fatty,  152,  174. 

fatty  degeneration  of,   from  phosphorus 
poisoning,  585. 

hypertrophy  of,  121. 

hypoplasia  of,  329. 

weakness  of,  in  obesity,  176. 
Heart  muscle,  degeneration  of,  330. 

disease  of,  75. 
Heart,  hypoplasia  of,  329. 
Heat,  independent  sources  of,  2. 

loss  of,  in  metabolism,  25. 

production  of,  in  metabolism,  36. 
Heat  and  cold  in  metabolism  of  the  sick,  25. 
Heat  equivalents,  44. 
Hebeloma  poisoning,  600. 
Heberden's  nodes.  247,  248. 
Helminthiasis,  504,  522. 

distressing  symptoms  of,  524. 

prognosis  of,  550. 
Hematoblasts,  345. 
Hematogen,  342. 
Hematokrit,  287. 
Hematology,  304,  354. 
Hematomata,  491. 

diffuse,  437. 
Hematopoietic  apparatus  of  chlorotics,  329. 
Hematopoietic  function,  435. 
Hematopoietic  organs,  341. 

affection  of,  305. 
Hematopoietic  tissues,  363. 
Hematuria,  angioneurotic,  449. 

caused  by  parasitic  disease,  513. 

essential,  448,  449. 

gouty,  451. 

hemophilic,  449. 

idiopathic  renal,  444. 


Hematuria,  in  leukemia,  353. 

in  pregnancy,  450. 

unilateral,  446,  447. 
Hemeralopia,  419. 

transmission  of,  419. 
Hemoalkalimetric  test  of  alkalinity  of  the 

blood,  399. 
Hemocytometer,  282. 
Hemoglobin,  277. 

absorption  spectra  of,  288. 

consumption  of,  305. 

formation  of,  305. 

percentage  of,  in  anemia,  306,  312. 
in  purpuric  blood,  495. 

reduction  of,  288,  305,  306,  326,  327,  349. 
in  chlorosis,  325,  333. 

remedies  containing,  342. 
Hemoglobin  scale,  277. 
Hemoglobinemia,  288. 
Hemoglobinometer,  277,  325. 
Hemometer,  277,  279. 
Hemophilia,  413,  445,  446. 

amount  of  blood  loss  in,  426. 

autopsy  findings  in,  430,  433. 

appearance  of,  after  trauma,  429. 

blood  examination  in,  423,  424. 

blood-vessels  unruptured  in,  431. 

causes  of,  unknown.  430. 

congenital,  421,  428,  429. 

course  of,  434. 

development  of,  by  intermarriage,  421. 

diagnosis  of,  440. 

discovery  of,  at  operations,  434. 

geographical  distribution  of,  422. 

hereditary,  414,  415,  416,  417. 

human,  429. 

identity  of.  with  scurvy,  427. 

joints  in,  432,  439,  455. 

local,  448. 

origin  of,  425. 

prognosis  of,  451. 

prophylaxis  of,  452,  455. 

renal,  442. 

revealed  by  accident,  434. 

seat  of  hemorrhage  in,  435. 

stages  of,  438. 

statistics  of,  415. 

symptomatology  of,  434. 

three  forms  of,  440. 

transmission  of,  in  families  by  females, 
414-417. 

treatment  of,  452,  453. 


INDEX 


631 


Hemophilia  as  independent  disease,  427. 

as  toxic  infectious  disease,  427,  428. 
Hemophiliacs,  capricious  appetite  of,  428. 

care  of,  in  childhood,  453. 

choice  of  occupation  for,  453. 

diet  of,  453. 

early  death  of,  430,  434. 

longevity  of,  416. 

remarkable  blood  finding  in,  425. 
Hemophotograph.  27'.),  280. 
Hemoptysis  in  echinococcus  disease,  537. 
Hemorrhage,  arrest  of,  454. 

arthritic,  435,   111. 

conjunctival.  429. 

control  of,  by  zymo-plasma,  424. 

cutaneous,  409,  460,  471,  476. 

difficult  control  of,  437. 

embolic,    177. 

essential  renal,  445,  447. 

gastric,  451. 

internal,  336,  494. 

interstitial,  435,  436,  437. 

leopard   appearance   of  skin  caused   by, 
466. 

multiple  capillary.    165. 

occurrence  of,  after  extraction  of  teeth, 
I.V.-.    154. 
in  hemophilia.    123. 
in  progressive,  pernicious  anemia,  314. 
in  scurvy,  399,    »01,    101.    »It«.), 
without    external  cause,    136. 

prodromes  of,    135. 
pulmonary.    151,    194. 
renal.    111.    117.    150,    151. 
retinal.   308,   31  1.    178,    188,    194. 

spontaneous,  1 1  1.  129,  130,  136. 
superficial,   135,   136. 

toxir,     !_".». 

traumatic,  n  I,  129,  136,   137. 
treatment  of.   197. 
[Hemorrhages,    Local,    upon    a    hemophilic 

baMs,    1  12. 
stria'-like,    172. 

Hemorrhagic  diathesis,  388,   177. 
<>i  leukemics,  353,  355. 

of  the   new  born,    IUI . 

1  [emosodium-urate,   127. 

1  lemosporidia,  606. 

Henoch's  purpura,  162,  I7'.t.  181,  182    (05 

Hereditary  transmission  of  disease,  1 1">.  116, 

117 
Herpätisme,  252,  21 


Heterogeny,  545. 

Hexathyridium,  514. 

"  Hexenschuss,"  139. 

Hexose,  oxidation  of,  265. 

Hippocrate-,  description  of  peliosis  by,  473. 

treatment  of  obesity  by,  152. 
Hirschfeld  on  antifat  cures,  56. 
Hirschfeld's  diet  rules,  174. 
Hirudines,  565. 
History  of  gout,  126. 

of  scurvy,  388. 
Hodgkin's  disease,  370. 

clinical  picture  of,  372. 

course,  duration,  and  outcome  of,  378. 

diagnosis  of.  375. 

hereditary  predisposition  to,  377. 

local  symptoms  of.  372. 

therapy  of,  378. 
Hoppe-Seyler-Tigerstedl  apparatus,  8. 
Host,  parasitic,  sutoinfection  of,  551. 
Hot-air  bath,   influence  in  metabolism,  '_'.">. 
House-fly,  as  disseminator  of  parasites,  503. 
1  lunger  cure,  161,  17">. 
Hurry  of  life,  a  cause  of  chlorosis,  333. 
Hydatid  echinococcus,  528. 

resonance,  533. 

thrill,  532, 540. 
Hydrochloric  acid,  action  on  pentose,  265. 
Hydrogen,  arseniurctcd.  poisoning  by,  5N7. 

Bulphureted,  poisoning  by,  586. 
Hydronephrosis,  541. 
Hydrops  tuberculosis  fibrinosus,  139. 

Hydrotherapy   in   diabetes,    122. 

in  obesity,  1 7">.  176 
modern,  310. 
I [ygiene,  errors  in.  306. 
general,  331. 
ignorance  of  principle-  of.  :;  i:; 

lack  of.  among  earth  worker-,  562. 

a-  cause  of  chlorosis,  333. 
observance  of.  in  Hodgkin's  dues  ■ 
Hymenolepis    (drepanitotajnia)    lanoeolata, 

Bloch,  519. 
Hyperacidity  of  stomach,   17. 
Hypercompensation,  88. 
Hyperemia,  258 

lly|MM'Lrl"l>nlia,    283 

Hyperglycemia,  diabetic,  7s.  86. 

1 1>  perglycosuria,  7^ 

Hyperhidrosis,  251. 

Hyperleukocyto 

Hypernutritioi  er-uutritioa 


632 


INDEX 


Hyperplasia,  acromegalic,  240. 

altruistic,  241. 
Hypertrophy  of  soft  parts  in  acromegalia, 

237. 
Hypnosis,  as  cause  of  hysterical  polyuria, 

118. 
Hypnotism,  questionable  use  of,  122. 
Hypochondria  verminosa,  524. 
Hypoderma  bovis,  573. 
Hypodermoclysis,  saline,  497. 
Hypoleukocytosis,  302. 
Hyponutrition.     See  Under-nutrition. 
Hypophysis,  adenomata  of,  240. 

disease  of,  195. 

hypertrophy  of,  195. 

tumor  of,  232,  233,  235. 
Hypoplasia,  inactivity,  331. 
Hypoplasia  of  heart  and  vascular  system, 

329. 
Hysteria,  association  of,  with  diabetes,  117. 

combination  of,  with  chlorosis,  338. 

origin  of,   335. 

polyuria  in,  116,  118. 

stigmata  of,  117,  119. 

Sydenham's  views  of,  340. 

symptom-complex  of,  336. 


Ileus,  causes  of,  370. 

lmmermann-Oertel  theory  of    hemophilia, 

427,  437. 
Inactivity  of  intestines,  intervals  of,  9. 
Inanition,  148. 

producing  fever,  30. 
Infarcts,  hemorrhagic,  401. 
Infection,  conveyance  of,  by  food,  509. 
by  mice,  571. 
by  water-cress,  509. 
through  wounds,  478. 
leukemia  caused  by,  356. 
morbus   maculosus  caused  by,  459,  460, 
461. 
Inflammation,  pulmonary,  339. 
Influenza,  a  cause  of  gout,  127. 
combined  with  scurvy,  396. 
occurrence  of,  in  chlorotics,  339. 
Infusoria,  506. 

Ingesta  and  excreta  compared,  6. 
Innervation  apparatus,  205. 
Inosite,  112. 


Insane,  muscular  action  in  the,  44. 
Insects,  parasitic,  571. 

parasites  propagated  by,  503. 

sting  of,  575. 
Insomnia,  324. 

in  trichinosis,  558. 
Inspiratory  furrow  in  liver,  540. 
Intermarriage,  debilitation  by,  253. 

influence   of,   among   hemophiliacs,   415, 
421. 

of  relatives  favoring  disease,  452. 
Internal  secretion,  absence  of,  199. 
Intervertebral  ganglia,  disease  of,  216. 
Intestines,     abnormal     decomposition     in, 
335. 

activity  of,  323. 

autointoxication  from,  335. 

paresis  of,  219. 

leukemic  infiltration  of,  351. 
Intestinal    canal,    assimilation   of   food   in, 

45. 
Intiina,  fatty  degeneration  of,  431. 
Intoxication,  acid,  399,  581. 
Inunctions,  splenic,  386. 
Iodin,  ingestion  of,  42. 

poisoning  by,  584. 

use  of,  in  therapy  of  Hodgkin's  disease, 
379. 
in  therapy  of  leukemia,  368. 
Iodothyrin,  189. 
Iridocyclitis,  252. 
Iritis,  252. 
Iron,  food  rich  in,  309. 

inorganic,  341. 

use  of,  in  anemia,  309. 
in  gout,  149. 

in  morbus  maculosus,  497. 
Iron  chlorid,  action  of,  on  adrenals,  209. 

in  hemophilia,  453. 
Iron  springs  of  Europe,  343. 

of  Germany,  342,  343. 
Iron  therapy  in  chlorosis,  340,  341. 
Ischiagra,  125. 
Isodynamic   action   of   carbohydrates   and 

fats,  51. 
Isodynamics,  law  of,  5. 
Isolation  in  treatment  of  diabetes,  124. 
Israel's  case  of  acromegalia,  240. 
Itch,  eruption  with,  565. 
Itching  disease,  599. 
Itching,  in  scabies,  567. 
Ixodes  ricinus  Linne,  566. 


INDEX 


633 


Jaundice  in  phosphorus  poisoning,  585. 
Jaw,   hyperplasia   of,  in   acromegalia,  235, 
236. 

periosteum  of,  in  scurvy,  403. 
Jecorin,  209. 

Joint,  hemophilic,  4:32,  430.  455. 
Joint,  of  knee,  puncture  of,  455. 
Joints,  affection  of,  secondary,  478. 

disease  of,  types  of,  244. 

effusions  of,  in  scurvy,  399. 

hemorrhages  into,  429. 

in  rheumatism,  24  I. 

inflammation  of,  125. 

puncture  of,   !">•). 

stiffness  of,  217. 

swellings  of,  in  purpura,  471. 

symptoms  of ,  in  gout,  132,  136. 

tuberculosis  of,  258. 


[Catherine  of  Arragon's  Balad,  398. 

Keratitis  from  scabies,  567. 

Kidney,  amyloid,  simulating  diabetes,  121. 

circulation  of,   12.'{. 

coccidiosis  of,  506. 

contracted,  altered  function  of  kidney  in, 
112. 
differentiated  from  diabetes,  121. 
echinococcua  of,  541. 

float  iriL'.    I'.n. 

functional  distui bance  of,  128. 
genuine  conl  racted,  I  12. 
increased  excretion  of  water  by,  ill. 
insufficiency  of,  132. 
necrosis  of.  m  goul .  I  12. 
neoplasm  of,  150. 

normal,  hemorrhage  from,  146,  117. 
parenchymatous  inflammation  of,  :w<>. 
Kisch's  cure  for  obesity,  177. 

Knee,  gOUty  at  tack  in,   135. 
still'.  Iron,  gout,    128. 

Koch's  theory  of  hemophilia,  128. 
Kolb's  views  of  purpura,  189. 

's  views  of  hemophilia,   138 

Koppe's  method  of  m I  examination,  287. 

Kreatinin   1 12. 

Kribbelkrankheit,  509. 

Krug'a  experiments  in  feeding,  15,  17. 


Kyphosis  of  acromegalia,  235. 
of  shoulder  and  hip,  246. 


L-arabinose,  264. 

L-xylose,  264. 

Lactose,  78. 

Lactosuria,  77. 

Lancereaux's  views  of  rheumatism,  252. 

Larrey,  observations  of,  on  obesity,  151. 

Larynx,  echinococcus  of,  536. 

gout  in,  142. 
Lavoisier's  study  of  chemical  processes,  2. 
Law  of  the  conservation  of  energy,  2.  53. 

of  the  development  of  the  surface,  5. 

of  the  permutation  of  forces,  2. 
Lead  acetate,  in  diabetes,   123. 

Lead  colic,  587. 

Lead  line,  588,  590. 
Lead  poisoning,  131,  587. 
Lecithin  in  adrenals,  209. 

Lemon  cure,  of  gout,  1  18. 

of  hemophilia,   lö.'l. 
Leontiasis  ossea,  ~'M\. 

Leprosy,  071. 

Leptus  autumnalis,  Shaw,  565. 

Leucin,  209. 

Leukanemia,  357,  362. 

Leukemia.  3  l">. 

acute,  cutaneous   hemorrhages   in.    Isö. 
autopsy  report-  of.  359. 

blood-changes  in.  :;  iv 

Mood  examination-  in,   :!.*>s.  360. 

causes  of.  :;.">7. 

diagnosis  of.  Hi'.»,  364,  :w>. 

fatal  course  of.  367. 

fever  in.  352. 

leukocyte,  350,  354,  355. 

local  t reat men!  of,  368 

lymphatic,  303,  .V.o.  351,  354 

myelogenous,  302,  350,  •';■">  1. 

parasites  found  in. 

pat hogenesis  of,  363. 

prognosis  of.  .",1.7 

proportions  of  Mood  corpuscles  ii 

specific  poison  a-  cause  of.  356. 

splenic-medullary,  35 1 

symptoms  "i   3  18. 

true  378 

I  oat  merit    of. 

varict  h  -  .it.  .;  19, 


634 


INDEX 


Leukocytes,  basophilic,  347. 

condition  of,  in  chlorotic  blood,  326. 

large  mononuclear,  297. 

mononuclear,  346,  356. 

morphology  of,  349. 

neutrophilic  polynuclear,  346. 

normal  proportion  of,  349. 

polynuclear  neutrophilic,  297. 

reduction  of,  312. 
Leukocytosis,  301,  302,  303,  344,  347. 

Addison's  disease  accompanied  by.  204. 

phenomenon  of,  303. 

post  hemorrhagic,  328. 

trichinosis  accompanied  by,  557. 

varieties  of,  364. 
Leukopenia,  302,  385. 
Leukorrhea  from  parasites,  551. 
Levulose,  109. 
Levulosuria,  77,  262. 
Letzerich's  views  of  purpura,  460. 
Leydenia  gemmipara  Schaudinn,  506. 
Lice,  of  body,  clothes,  and  head,  501,  571, 

572. 
Life  insurance  and  obesity,  157,  160. 
Life  insurance  and  pentosuria,  271. 
Life,  mode  of,  as  cause  of  disease,  333. 
favoring  chlorosis,   339. 
unhygienic,  332. 

process  of,  a  mystery,  49. 
Ligamenta  lata,  echinococcus  in,  543. 
Lind's  description  of  scurvy,  391. 
Linguatula,  570. 

Lip,  hemorrhagic  prominence  of,  483. 
Lipoma  arborescens,  249. 
Lipomatosis  cordis,  152. 

universalis,  152,  154. 
Liver,  abscess  of,  540. 

alcoholic,  383. 

cirrhosis  of,  43,  382.' 

coagulation  necrosis  of,  489. 

condition  of,  in  splenic  pseudo-leukemia, 
382. 

echinococcus  of,  530,  531,  534. 

enlargement  of,  351. 

functional  disturbance  of,  140. 
Liver,  as  food,  forbidden  in  diabetes,  99. 
Liver-fluke,  508. 

in  various  parts  of  body,  510. 
Living  cell  substance,  41. 
Lithia,  salts  of,  257. 
Lithium  in  gout,  148. 
Löwit's  researches  in  leukemia,  356, 


Longevity  of  the  obese,  157. 
Lumbago  in  gout,  146. 
Luxury  consumption,  10,  53. 
Lungs,  echinococcus  of,  537. 

hemorrhagic  edema  in,  401. 

hypostatic  congestion  of,  401. 
Luthje's  experiments,  16. 
Lymph-formation,  anomalies  of,  335. 
Lymph-glands,  adhesion  of,  376. 

enlargement  of,  351,  370. 

internal,  enlargement  of,  372. 

lymphocyte  production  in    348. 

rupture  of,  376. 
Lymph-vessels,  echinococcus  of.  539. 
Lymphadenoid  proliferations,  375. 
Lymphadenoma,  339. 
Lymphangitis,  143. 
Lymphatic  trunks,  displaced,  373. 
Lymphemia,  acute,  355. 
Lymphocytes,  293,  296,  302,'  346,  382. 

increase  of,  361. 
Lymphocythemia,  382. 
Lymphocytosis,  365,  366. 
Lymphomata,  384. 

leukemic,  375. 
Lymphomatosis,  372. 
Lympho-sarcomatosis,  375,  377. 
Lye,  poisoning  by,  582. 


M 

Macrocytes,  299. 

Macroglossia  in  acromegalia,  236. 
Maggots.     See  Fly-larva1 . 
Magnus-Levy,  experiments  of,  23. 

researches  of,  in  metabolism,  34. 
Maintenance  of  life,  law  of,  5. 

on  low  nutrition,  53. 
Mal  de  sol,  599. 
Malaria,  blood  examination  in,  291. 

enlarged  spleen  in,  384. 

melanotic  discoloration  from,  383. 
Males,  hemophilia  in,  415. 
Malnutrition,  161. 
Malperforant,  85. 
Maltose,  262. 
Maltosuria,  271. 
Mange  of  animals,  567. 
Marasmus  in  cocainism,  597. 
Marriage,  of  chlorotic  girls,  338. 

of  hemophiliacs,  452. 


INDEX 


635 


Mi -sage,  66. 

in  chlorosis,  340,  3-11. 

of  spleen,  386. 
Mast-cells,  298,  347,  355. 
Heals,  <l;iily  number  of,  171. 
Meat,  compulsory  inspection  of,  533. 

decomposed,  poisoning  from,  601. 

fresh,  a  preventive  of  scurvy,  395. 

kind  and  amount  of,  in  diet  of  diabetics, 
99,  108. 

of  poisonous  animals,  601. 

prevention  of  infection  by,  525.  554. 

salt,  as  cause  <>f  scurvy,  397,  398,  411. 

value  of,  in  diet,  74. 
Mediastinum,  echinococcus  of,  538. 
Medical  Congress,  Paris,  1900,  126,  127. 
Medication  in  anemia,  309. 
Medicine,   Internal,  Congress  of,  56. 
Medullin,  197. 
Megaloblasts,  300,  311. 

in  anemia,  31 1. 
Megalocytes,  299,  300. 
Melanotic  discoloration,  383. 
Memory,  failure  of,  in  anemia,  314. 
Men,  chlorosis  in,  329,  330. 

development  of  frit  in.  159. 
Meningitis,  tubercular,  in  Addison's  disease, 

225. 
Meningocele  congenita,   128. 
Menopause,  hematuria  accompanying,   150. 

obesity,  a-  caused  by,  155. 

occurrence  of  rheumatism  during,  245. 

use  of  oöphorirj  in.  L55,  196,  L97. 
Menstruation,  abnormalities  of.  333. 

condition  of.  in  chlorosis,  32  I. 
in    hemophiliacs.    435. 

disorders  of,  use  <>t  oöphorirj  in.  I(.i7. 
Mental  changes,  in  myxedema,  185. 
Mentholglycuronic  .nid.  26  I. 
Mercury,  poisoning  by,  587,  589. 
Mesentery,  echinococci  of,  542. 
Metabolism,    Caspari's    investigations    in, 
51. 

chemical  processe    of,  1. 

condition  of,   in  children 

in  chlorosis,  323. 

in  gout,    12. 

in  progressive  pernicious  anemia,  313. 
diagram  of,  35. 

disturbance  of,  in  myxedema.   185. 
experiments  in,  of  Kaj  ser,  21. 
from  dynamic  point  of  \  ie* .  19 


Metabolism,  hereditary  weakness  of,  82 

increased,    192. 

intermediary,  53. 

Krug's  experiments  in,  61. 

limited  labor  of,  in  diabetes,  96. 

modern  laws  of,  4. 

perversion  of,  32. 

proportion  of,  to  body  surface.  ■'>. 

quantitative  analysis  of  disturbances  of, 
1,  4,  37. 

quantitative  estimation  of,  8. 

ratio  of,  in  rest,  5. 

researches  in,  of  Bischoff,  56. 
of  Jaquet,  35. 
of  Lüthje,  40,  41,  56. 
of  Rulmer.  36. 
of  Sonden,  36,  37. 
of  Tigerstedl .  30,  37. 

respiratory,  4,  25. 

slowing  of,  26,  31. 

stimulation  of,  343. 

sugar.  207. 

total  energy  of,  22. 

toxic  products  of,  207. 
Metachromasia,  298. 
Metallic  salts,  poisoning  by,  587. 
Metalloids,  poisoning  l>y,  582,  583. 
Metals,  alkaline,  poisoning  by, 
Metamorphosis,  direct,  545. 

Methe globin,  287. 

Microblasts,  307. 

Microcytes,  299,  326. 

Miescher's  tubes,  506. 

Migraine  in  gout .  I  13. 

Milk,  condensed  Swiss,  for  infants,  is7. 

Pasteurizal  ion  of,  186. 

value  of,  for  chlorotics,  341. 
in  diet  of  diabetic-.  100,  108. 
in  acid  toxicosis,   ">sl. 
Milk-sugar.  78,  262. 
Mineral  spring  cures,  I  Is- 

for  Hodgkin's  disease,  379. 

in  rheumatism,  258 
Minute-kilo-values  in  metabolism,  34. 

Mitchell.  S  Writ,  on  treatment  of  neuras- 
thenia and  hysteria,  65 

Mode  of  life  as  cause  of  goul .  I 

Monkey-,  experimental  production  ofscurv y 
in.  394. 

Monoarthril  is,  senile 

Monosodium  urate.  127. 

Monoetomum  lentis,  Nordmann,  •'>!  l. 


636 


INDEX 


Morbus  maculosus  Werlhofii,  414,  425,  457. 

autointoxication  a  cause  of,  459. 

autopsy  report  of,  484. 

bacteriology  of,  489,  490. 

composition  of  blood  in,  494. 

confounding  of,  with  typhus,  482. 

cutaneous    hemorrhages    accompanying, 
464. 

diagnosis  of,  484. 

distinction  of,  from  scurvy,  458. 

etiology  of,  459,  477. 

febrile  phenomena  in,  494. 

frequency  of,  in  youth,  480. 

infectious,  459,  460,  461. 

intestinal  symptoms  in,  492,  493. 

nervous  shock  a  cause  of,  468. 

occurrence  of,  after  fright,  462. 

pathological  anatomy  of,  487. 

predisposing  cause  of,  480. 

prognosis  of,  in  children,  481. 

prophylaxis  of,  496. 

relapses  of,  461. 

special    symptomatology  of,  481,  490. 

stages  of,  480. 

temperature  in,  472. 

treatment  of,  496. 
Morphin  habitues,  271. 

Morphin,  poisoning,  acute  and  chronic,  595. 
Morphinism,  271,  443. 
Motor  disturbances  in  chlorosis,  324. 
Mountain  climbing,  67,  72. 
Mouse  septicemia,  571. 
Mucous  gland,  tumor  of,  238. 
Mucous  membrane,  catarrh  of,  140. 

condition  of,  in  scurvy,  400. 
Mucous  membrane  of  mouth,  in  Addison's 

disease,  201. 
Mucous  membrane   of  respiratory  organs, 

142. 
Murmurs,  anemic,  321. 

functional,  321. 

hemic,  321. 

nun's,  322. 

organic,  321. 

venous,  322. 
Muscides  larvse,  574. 
Muscle,  accumulation  of,  55. 

increase  of,  57. 
Muscle  lameness,  sympathetic,  556. 
Muscles,  activity  of,  53. 

condition  of,  54. 

electric  contractility  of,  558. 


Muscles,  excision  of,  in  trichinosis,  559. 

free  movement  of,  331. 

loosening  of,  by  scurvy,  400. 

resemblance  of,  to  smoked  goose  breast, 
558. 

swelling  of,  in  trichinosis   557. 

work  hypertrophy  of,  57. 
Muscular  labor,  forced,  52. 
Muscular  power,  source  of,  15,  51. 
Muscular  tension,  effect  of,  44. 
Muscular  tonus,  30. 

Musculature,    increase    of,   in  acromegalia, 
236. 

trichinae  in,  554. 
Mushroom  poisoning,  585,  600. 
Mussels,  poisoning  by,  600. 
Myelin,  20.9. 
Myelocytes,  300,  347. 

production  of,  360. 
Myiosis,  573. 

intestinalis,  574. 
Myopathy,  progressive,  195. 
Myositis,  acute  fibrous,  248. 
Myxedema,  30,  179,  188. 

abortive,  192. 

autopsy  reports  of,  186- 

etiology  of,  180. 

infantile,  187. 

pathology  of,  186. 

relapses  of,  193. 

sensations  of  cold  in,  185. 

substitution  therapy  in,  225. 

symptoms  of,  180. 

temperature  in,  185. 

therapy  of,  188. 

thyreoiodin  in,  189,  193,  195. 
"Myxoedeme  fruste,"  191,  192. 


N 

Nansen  Expedition,  absence  of  scurvy  in, 

393,  411,  412. 
Nasal  cavity,  inflammation  of,  377. 
Natural-Healer,  60. 
Nature-cure  institutions,  60. 
Nausea  caused  by  fat,  167. 
Neck,  echinococcus  in,  535. 

enlarged  glands  of,  371. 
Necrosis  of  jaw  in  scurvy,  403. 
Needle  baths,  257. 
Nematoda,  544. 


INDEX 


637 


Nematodes,  perforation  of  ulcers  by,  549. 
Nephrectomy,  447. 

for  renal  hemophilia,  443. 
Nephritis,  142,  451. 
chronic,  337. 

differentiated  from  diabetes,  121. 
in  rheumatism,  252. 
interstitial,  498. 
metabolism  in,  41,  42. 
parenchymatous,  449. 

in  trichinosis,  558. 
unilateral,   1 IÖ. 
Nephrolithiasis,  1 19. 

Nerve  areas  connected  with  adrenals,  222. 
Nerve  elements,  204. 
Nervines  in  diabetes,  93. 
Nervous    symptoms    in    Addison's    disease, 
200,  211.  218. 
in  chlorosis,  32  1. 
Nervous  system,  central,  255. 
disturbances  of,  313. 
in  anemia,  315. 
changes  in,  in  Addison's  disease,  215. 
condition  of,  in  acromegalia,  238. 

in  gout,  1  I'-. 
disease  of,  a  cause  of  Addison's  disease, 
213. 
simulating  adrenal  disease,  219. 
hereditary  affection  of,  126. 
Neuenahr,  treatment  at,  101. 
Neuralgia,  gouty,  I  !•'■ 
intercostal,  32 1. 
local  pressure  a-  cause  <>f,  373. 
occurrence  of.  in  chlorosis,  324. 
Neurasthenia,  under-nutrition  resulting  in, 
ei). 

value  of  fat   in.  55. 

Neurasthenic  conditions.  1  12. 
Neuritis,  in  gout .  I  13. 
Neuropathic  constitution,  1 15. 
Neuropathic  predisposition,  Hi. 
Neuroses,  combination  of,  with  corpulence, 
i -.'.). 
fund  ional,  1 16. 
eral,  I  12. 
Neurosis  of  \  asomotors,  336. 
\ciit ral  dyes,  staining  in,  297. 
Neut rophiles,  355. 
Neul  rophilic  leukocj  I 
Neutrose,  18. 

Newcastle  mi  '1'vne.    lead    poisoning      ' 

Nicotin  poisoning,  acute  and  chronic,  595. 


Night-blindness,  etiology  of,  419. 
Nitrodxmzol,  poisoning  by,  592. 
Nitrogen,  elimination  of,  12,  42,  43. 

estimations  of.  in  \c<-c^,   !.">. 

loud  substances  free  from,  71. 
retention  of,  17. 
Nitrogen  accumulation,  19. 

Nitrogen-balance,  37. 
Nitrogen  equilibrium,  7,  20.  29. 

Nitrogen  excretion  in  the  urine,  11. 
Nodules,  caused  by  Glarise,  •">  18. 
Nodules,  gouty,  137,  138. 

lymphatic,  352. 
No-fat  cure,   103.   165. 

Noorden-Dapper  on  antifal  cures.  50. 
Normal  proportions  of  blood-corpuscles,  283, 

284. 
Normoblasts,  300,  307.  356. 

shower  of,   in    blood    after    hemorrhage, 
328. 
Normocytes,  299. 
Nose,  copper,  in  gout,  1  13. 

echinococcus  in,  535. 

expulsion  of  oxyuris  from.  551. 

parasitic  di~e:ise  of,  574. 
Nose  bleed,  120. 

Nostalgia  a-  cause  of  chlorosis,  333. 
Nourishment  during  antifal  cures,  56. 
Nuclein,  atypical,  266. 

f I  rich  in,  137. 

pancreatic,  207. 

Nudeinic  acid,  265,  267. 

Nucleins,  animal,  265. 

Nucleo-proteids,  266. 
Nursing,  in  morbus  maculosus,  lor. 
of  chlorotic«,  3  \0. 

Nutrition,  condition  of,  5  I 

conducing  to  chlorosis, 
general  disturbance  of.  206. 

individual  standard  "I.  55. 

laws  "i.  i 

in  carnh  ora,  I 
medium  Btate  of,  55,  59 

Opl  imuiii  of,  tili 

processes  of,  •"><•. 
rational  i  herapy  "f.  i . 
Nutrition,  in  morbus  macul 
of  convalescents,  -il , 
ol  fever  patients,  31 . 

.if  the   rid 

Nutritive  preparations,  70. 
Nutrose,  7ii. 


<;;;s 


INDEX 


Nyctotherus  faba,  508. 
Nylander's  test,  262. 


O 
Obesity,  151. 

after  menopause,  1.55. 

after  pregnancy,  155. 

alcohol,  a  cause  of,  155. 

association  of,  with  gout   and   diabetes, 

154. 
Banting  cure  of,  70,  72,  73,  74,  163,  164, 

165,  166,  173,  175. 
calory  requirement  in,  35. 
clinical  cases  of,  171. 
combination  of,  with  gout,  171. 
complications  of,  69.  156. 
composition  of  urine  in,  157. 
constitutional,  35. 
cure  of,  by  thyreoiodin,  194. 
dangers  of  rapid  reduction  of,  68. 
Debove's  treatment  of,  161. 
degrees  of,  68. 
diagnosis  of,  159. 
diet  in,  161. 

economy  of  food  material  in,  34. 
effect  of,  on  life  insurance,  158. 
effect  of  perspiration  in,  26. 
etiology  of,  62,  153. 
example  of,  151. 
fluids  unlimited  in,  75. 
functional,  156. 
gout,  as  caused  by,  130. 
Harvey's  cure  of,  70,  72,  163,  165. 
in  ancient  times,  151,  152. 
influence  of,  upon  feminine  fertility,  152. 

on  mental  powers,  159. 
metabolism  in,  34. 
muscular  exercise  in,  173. 
occurrence  of,  in  convalescence,  155. 
of  adolescents,  154. 
of  eunuchs,  154. 
of  people  of  Munich,  155. 
of  the  healthy,  68. 
over-nutrition  a  cause  of,  57. 
plethoric,  62,  177. 
predisposition  to,  153,  154. 
prognosis  in,  157. 
relation  of,  to  gout,  144. 
slow  reduction  of,  170. 
stages  of,  155. 
thirst  in,  170. 


Obesity,  treatment  of,  160,  175,  176. 
by  depletion,  162. 

under-nutrition  in  cure  of,  59. 

value  of  exercise  in,  173. 

various  methods  of  cure  of,  70,  163. 

views  of  Ebstein  and  Oertel  on  reduction 
of,  56. 
Odor  of  scorbutic  fluid  and  tissue,  403,  405. 
Oertel  obesity  cure,  174,  175. 
Oertel's  views  of  hemophilia,  425. 
Oligsemia  vera,  330. 
Oligemia  combined  with  chlorosis,  338. 
Oligochromemia,  304,  326,  385! 
Oligocythemia,  185,  250,  325,  385. 
Oligoplasmia,  328. 
Omagra.  125. 

Omentum,  echinococcus  of,  543. 
Onychia  scorbutica,  405. 
Oöphorin,  use  of,  during  the  menopause,  155, 
196,  197. 

for  menstrual  difficulties,  197. 
Open  air  exercise,  67. 
Ophthalmia,  metastatic,  459. 
Opium  poisoning,  acute  and  chronic,  595, 

596. 
Opium  smokers  of  China,  589. 
Opotherapy,  196. 
Oral  cavity,  amebae  in,  505. 

bacilli  in,  378,  394,  395. 

echinococcus  in,  535. 

foul  odor  from,  403. 
Orbit,  echinococcus  of,  535. 
Orcin  test,  263,  272. 
Ord's  cases  of  myxedema,  179. 
Organic  diseases,  331. 
Organism,  process  of  life  in,  a  mystery,  49. 

waste  in,  12. 
Organotherapy,  189,  196,  224. 

employment  of,  since  antiquity,  196. 
in  acromegalia,  242. 
in  anemia,  319. 
in  leukemia,  368. 

practice  of,  in  China,  196. 

review  of,  197,  198. 
Organs,  blood-forming,  310. 
Orthopedic  treatment,  259. 
Orthopnea,  352. 

Osteoarthropathy,  hypertrophic,  240. 
Osteomyelitis,  257. 
Ovarian  extract,  155,  196,  197. 
Ovarian  therapy,  155,  196,  197. 
Ovaries,  echinococcus  of,  543. 


INDEX 


639 


Over-nutrition,  54. 

accumulation  of  fat  in,  59. 

amount  of  food  necessary  for,  59. 

best  method  of,  70. 

combination  of,  with  hard  manual  labor, 
62. 
with  muscular  exercise,  58. 

consequences  of,  61. 

in  Basedow's  disease,  65. 

in  chronic  wasting  diseases,  63. 

in  diabetes,  64. 

in  exophthalmic  goiter,  64. 

in  functional  nervous  diseases,  65. 

in  pulmonary  tuberculosis,  63. 

in  syphilis,  63. 

indications  for,  62,  66. 

occurrence  of,  61. 

technic  of,  69. 
Oxalic  acid  toxicosis,  581. 
Oxidation,  changes  in,  in  disease,  43. 

deficient,  in  myxedema,  Is". 

degree  of,  22. 
alter  muscular  labor,  24. 
in  fever,  30. 

diminished,  34. 

increase  of,  by  hot  water  bath,  2.">. 

secondary,  '»I . 
(  brybutyric  arid  in  urine,  91. 
Oxygen,  consumption  of,  8. 

inhalations  of,  in  leukemia,  litis. 

intake  (it,  s. 

treatment  by,    197. 

( Ixyuriasis,  diagnosis  of,  552. 

treatment  of,  552. 
Oxyuris  host,   551. 

vermicularis,  Limn',  548,  550. 
Oysters,  poisoning  by,  600. 


Pain  in  Addison's  disease,  218. 

in  gout,    126. 
Palate,  gangrene  of,   179. 
Pallor,  general,  in  chlorosis,  336. 
Palpitation,  cardiac, 
Pancreas,  carcinoma  "t\  16. 

condition  <>t\  in  acromegalia 

diseases  of,  as  cause  of  diabetes,  82,  8 1. 

echinococcus  of,  541. 

extirpation  of,  producing  diabetes,  Bl. 

relation  of,  to  glycosuria,  196. 


Pancreas  proteid,  266. 
Pancreatic  juice,  action  of,  46. 

occlusion  of,  46,  47. 
Panophthalmia,  '>'■>■'>. 
Parablasts,  417,  418. 
Paracentesis,  43. 
Paralyses  in  the  obese,  69. 
Paralysis,  gouty,  143. 

Parasites,  anemia  caused  by,  309. 

animal,  distribution  of,  502. 
sexual  maturity  of,  502. 
varieties  of,  501. 

asexual  forms  of,  502. 

blood-suckim:.  ."»ii_'. 

development  of,  502. 

intestinal,  39. 

health  not  injured  by,  521. 

occasional,  .">()1 .   ~>7~>. 

permanent.  501. 

tenacity  of  life  of,  520. 

virulent  form  of,  574. 
Parasites  of  man,  499. 

amebae,  505. 

balantidia,  508. 

cilia,  508. 
coccidia.    506. 
distoma,  509. 
flagella,  507. 
helminthes,  508. 
infusoria,  507. 

megastoma  entericum,  -~>  < » T . 
plathelmintheSj  508. 
protozoa,  505. 
rhizopoda,  505. 
trichomonades,  507. 
vorticelli.  508. 
Parasitic    disease,    blood    examination    in, 
275. 

prevent  ion  of.  ."._'".. 

symptomatology  of.  503,  509. 
Qchymatous  injections,  386. 
Parotid,  echinococcus  in. 

Passive  exudation.  3i 

PediculUS   capitis,   de   <  . .  .  r     .".7  1  . 

l'eliosis  cachecticorum,  176. 
gonorrhoica,   179. 
rheumatica,  109,  169,  173,  174,   ; 
autopsy  findings  of,  isv 
Bamber  of,  176 

with  a  typical  course,   176. 
Schoenleinii,  i">7. 
Pellagra, 


640 


INDEX 


Pelvis,  true,  echinococcus  of,  543. 
Pentastoma  constrictum,  v.  Siebold,  570. 

taenioides,  Rudolphi,  570. 
Pentose,  77,  262. 

combustion  of,  265. 

dextro-rotary,  272. 

in  animals,  266. 
Pentosuria,  77,  262. 

alimentary  and  chronic,  268. 

caused  by  cherries,  plums,  beer,  77. 

in  morphin  habitues,  271. 

increase  of,  by  starches,  264. 

prognosis  of,  271. 

relation  of,  to  diabetes,  271. 

therapy  of,  271. 

typical  cases  of,  269. 
Pentosuria  and  life  insurance,  272. 
Peptones,  calories  in,  13. 
Pericardium,  echinococcus  of,  539. 
Peripheral  joints,  gout  in,  136. 
Peripheral  nerves,  degeneration  of,  216. 
Peristalsis,  intestinal,  207. 
Peritonitis,  tubercular,  47. 
Perityphlitis,  examination  of  blood  in,  303. 
Pernicious  anemia,  39,  47,  305,  314,  382. 

metabolism  in,  33. 

parasites  as  cause  of,  504. 

presence  of  tape-worms  a  cause  of,  523. 

toxic  influence  inducing,  316. 
Perspiration,  insensible,  26,  113,  184. 
Perspiration,  sensible,  26. 
Pes  varus  congenitus,  428. 
Petechise  in  scurvy,  404. 
Pettenkofer  respiratory  apparatus,  154. 
Peyer's  patches,  in  purpura,  487. 
Pharmacodynamics,  197. 
Phenol  poisoning,  593. 
Phenylhydrazin  test,  262,  263,  264. 
Phenylosazone,  265. 
Phlegmons  of  gout,  134. 
Phloridzin  poisoning,  83. 
Phloroglucin  test,  263,  265. 
Phosphorus  in  dejecta,   chemical  proof  of, 

585. 
Phosphorus,  retention  of,  18. 
Phosphorus  poisoning,  584. 

chronic,  586. 
Photography  in  case  of  acromegalics,  231. 
Phthirius  inguinalis,  Redi,  572. 
Physaloptera  caucasica  n.  spr.,  564. 
Physical  exertion,  influence  of,  on  metabo- 
lism, 24. 


Physical  remedies,  257. 

Picric  acid  poisoning,  593. 

Pierre  Marie's  study  of  acromegalia,  229. 

Pigment  in  blood,  292. 

Pigment,  pathologic  deposition  of,  213. 

Pigmentation  of  skin,  200. 

Pilocarpin,  in  diabetes,  123. 

Pimelosis,  152. 

Piperazin  in  gout,  148. 

Piperin  in  pseudo-leukemia,  386. 

Pituitary  body,  195. 

in  acromegalia,  238. 
Placental  area,  diphtheria  of,  478. 
Plagiomonas  urinaria,  507. 
Plasma,  accumulation  of,  in  blood,  335. 
Plasmon,  48,  70. 
Plaster    of    Paris,    for    hemophilic    joints, 

456. 
Playfair-Mitchell  treatment  of  neurasthenia, 

58,  65. 
Plerocercoides,  520. 
Plethora,  341. 

hemorrhage  as  caused  by,  437. 

hydremic,  425. 

serosa,  121. 

vera  seu  sanguinea,  156. 
Pleura,  ecchymoses  upon,  557. 

echinococcus  of,  536. 

inflammation  of,  373. 
Pleural  effusions,  373. 
Plica  polonica,  571. 
Pliny  on  corpulence,  163. 
Pliny's  rules  for  obesity,  152. 
Pneumonia,  central,  291. 

followed  by  purpura,  482. 
Poisoning,  acid,  579,  581. 

agaricus  muscarius,  600. 

alkaloid,  594. 

anilin,  592. 

animal,  598. 

antipyrin,  594. 

arnican,  598. 

arsenical,  586. 

atropin,  597. 

balsam  of  copaiba,  594. 

barium,  5S3. 

bromin,  584 

camphor,  594. 

carbolic  acid,  593. 

carbonic  oxid,  590. 

chloral  hydrate,  584. 

chloroform,  584. 


INDEX 


641 


Poisoning,  Cocain,  597. 
comutin,  598. 
digitalis,  597. 
endogenous,  579. 
ergot,  598. 
ethyl  alcohol,  591. 
exogenous,  579. 
fish,  600. 
590. 
iodin,  584. 
lead,  587. 
meat,  600. 
mercurial,  5X7.  5X9. 
morphin,  5'.»."),  596. 
mushroom,  5x0,  iioo. 

mussel,  (KM). 

nicotin,  595. 

nitro-benzol,  592. 

opium,  595,  596. 

oxalic  acid,  581. 

oyster,  600. 

phenol,  .")!»:$. 

phloridzin,  79. 

phosphorus,  ~>x 1. 

picric  acid,  593. 

prussic  acid,  582. 

salicylic  acid,  593. 

sulphonal,  591,  592. 

sulphur,  586. 

tetronal,  591,  592. 

toad-stool,  599. 

trional,  591,  592. 

vegetable,  598. 
Poisoning  caused  by  alkalies,  582. 

by  antineuralgics  and  antipyrel  ics,  5,.t'_>. 

by  arseniureted  hydrogen,  587. 

by  caffein  and  I hein,  595. 

by  chlorin  combinations,  583. 

by  lye,  582. 

by  metallic  Baits,  587. 

by  metalloids,  582,  5.x:?. 

by  potassium  chlorate,  583. 
I  'ockel  sped  roscope,  287. 
Podagra,  125,  1  l<>. 
Poikilocytosis,  299,  306,  312,  326. 
Polyuria,  111. 

after  trauma,  I  n*>. 

hysterical,  1 16,  1 18. 

permanent,   1  15,   I  19. 

pure  primary,  117,  118. 
t  ransitory,  1 15. 
underlying  cause  of,  L22. 
42 


Polyarthritis,  chronic,  253. 

primary  chronic  progressive,  246. 

sicca,  250. 

villosa,  244. 
Polychromatophilia,  326. 
PolychromatophUic  degeneration,  299,  307, 

312. 
Polycythemia,  185. 
Polydipsia.  111. 
Polynuclear  leukocytosis,  3G5. 
Polypionia  infantum,  154. 
Polyplasmia,  328. 
Polysarcia,  155. 

adiposa,  152. 
Pork,  containing  trichina,  553. 
Portal  vein,  disease  of,  3S3. 
Potassium,   deficiency   of,    causing   scurvy, 
399. 

acid  vegetable,  as  preventive  of  scurvy, 
11(1. 
Potassium  bromid,  in  diabetes,  1 22. 
Potassium  carbonate,  in  potatoes,  398. 
Potassium  chlorate.  583. 
Potassium  soap,  379,  380. 
Potatoes,  as  preventive  of  scurvy,  397,  398. 
Predisposition  to  diabetes,  XI),  94. 

to  gout,  126,  139. 

to  hemophilia.   1 1  1. 

to   scurvy,    390,  396. 

Pregnancy,  diabetes  insipidus  occurring  in, 
120. 

hematuria   in.    150. 

hemorrhages  of,  15  1. 

lactosuria  in,  79. 

psychical  influences  during,   121. 

Priapism  in  leukemia,  352. 
Pribram's    Statistics    of    rheumatism,     243, 
2  11. 

Priessnitz  pack,  25.x. 

Progressive    pernicious   anemia,    .'>().">,    .'Jio, 
359,  563. 
cardiac  symptoms  of,  313. 

course  of,  31 7. 

distinction  <>f,  from  various  diseases,  318. 

fatality  of,  317. 

prognosis  of,  ->I7. 
symptoms  of,  311,  313. 
Prophylaxis  in  diabetes,  93. 

in  hemophilia.    152 

Prostate  gland,  echinococci  of,  S  12. 
Proteid  metabolism,  1 1 ,  39 
Proteid  requirement  for  i  he  no! 


642 


INDEX 


Proteids,  identity  of,  2. 

Proteids  in  metabolism,  36. 

Protein  substances,  3. 

Protoplasm,  faulty  composition  of,  131. 

general  diseases  of,  139,  154,  157. 

granular,  346. 

production  of,  40. 
Protozoa,  505. 
Prurigo,  568. 

Pruritis  from  oxyuris,  551. 
Prussia,  cattle  disease  in,  533. 
Prussic  acid,  582. 
Pseudo-leukemia,  363,  370. 

clinical  picture  of,  377. 

lesions  of,  371. 

occurrence  of,  in  children,  385. 

treatment  of,  385. 
Pseudo-leukemia  lienalis,  371. 

lymphatica,  371. 

lymphatico-lienalis,  371. 
Pseudoparasites,  501. 
Psoriasis,  143,  253. 

linguae,  140. 
Psychic    functions    in    diabetes     insipidus, 

114. 
Psychical  anomalies  in  chlorosis,  324. 

in  diabetes  insipidus,  117. 
Psychical  causes  of  chlorosis,  332. 
Psychical  influences,  symptoms  of,  304. 
Psychosis,  acute,  591. 
Ptomain  poisoning,  a  cause  of  scurvy,  393, 

394. 
Puberty,  chlorosis  appearing  at,  330. 
Pulmonary  artery,  murmur  over,  in  chlor- 
osis, 321. 
Pulse,  in  anemia,  321. 
Pulse,  tension  changes  in,  121. 
Purpura,  changes  in  the  blood  causing,  463. 

changes  in  vessels  causing,  463. 

chilling  of  body  a  cause  of,  468. 

clinical  picture  of,  469. 

distinction  of,  from  various  diseases,  458. 

experimental  production  of,  461,  462. 

Henoch's,  462,  479,  481,  482. 

idiopathic,  489. 

mildest  forms  of,  471. 

relapsing,  468,  471,  492. 

remarkable  case  of,  483,  484. 

spontaneous  and  primary,  467. 

successive  attacks  of,  492. 

toxic  forms  of,  459. 

varieties  of,  457,  469. 


Purpura,  varieties  of,  abdominalis,  469,  479. 

cachecticorum,  465. 

dyspeptica,  469. 

fulminans,  467,  481. 

gonorrhoica,  469,  492. 

hemorrhagica,  457,  469,  471,  472. 

intestinalis,  471,  492. 

rheumatica,  457,  465,  469,  471,  473,  492. 

scorbutica,  471. 

simplex,  457,  467,  469. 

urticans,  457,  473. 
Pyelitis,  simulating  diabetes,  121. 
Pyemia  from  echinococcus,  532. 
Pyrocatechin,  209. 


Q 

Quinin  in  leukemia,  368. 
in  pseudo-leukemia,  385. 


R 

Rachisagra,  125. 
Rachitis,  459,  467,  485. 

treatment  of,  by  thyreoid  gland,  195. 
Radioscopy,  191. 
Rags,  parasites  in,  565. 
Rail-brace  apparatus,  456. 
Rainey's  tubes,  506. 
Rape,    attempted,    causing   morbus   macu- 

losus,  469. 
Rats  as  source  of  trichina  infection,  553. 
Rectum,  itching  of,  551. 

polypus  of,  513. 
Refrigeration  as  cause  of  purpura,  468. 
Regime,  antinervous,  340. 
Relapsing  fever,  spirilli  of,  291. 
Renal  diseases,  associated  with  obesity,  69. 
Renal  echinococcus,  533. 
Renal  epithelium,  449. 
Renal  gout,  primary,  132. 
Renal  hematuria,  essential,  445. 
Renal  hemophilia,  442. 

cases  of,  443. 

hereditary,  451. 
Renal    hemorrhage,   hemophilic,  treatment 
of,  444. 

congestive,  450. 

forms  of,  447. 
Renal   inflammation   combined   with  gout, 
137. 


INDEX 


643 


Renal  irritation  from  acid  toxicosis,  5S0. 
Resorts  for  treatment  of  dial>etes,  101. 

of  gout,  1  IS. 
Respiration,  difficult,  in  Hodgkin's  disease, 

373. 
Respiration  rate,  acceleration  of,  323. 
Respiratory  apparatus,  7. 

of  Hoppe-Seyler-Tigerstedt,  8. 

of  Zuntz  and  Geppert,  8. 
Respiratory  diseases  in  the  obese,  69. 
Respiratory  metabolism,  28,  34. 
Respiratory    organs,    inflammation    of,    in 

gout,  142. 
Respiratory  passages,  catarrh  of,  352 
Respiratory  quotient,  8. 
Rest  energy,  5. 

Rest  in  bed  for  neurasthenia,  05. 
Rest  in  treatment  of  chlorosis,  340. 
Rest  metabolism.  29. 
Real  values  in  metabolism,  24,  27,  32. 

tables  tor,  27. 
Restlessness,  influence  of,  in  metabolism,  1 1. 
Rete  sfalpighii,  pigmentation  in,  213. 
lift ina,  serous  infiltrations  of,  :;_'.". 
Retina]  hemorrhages,   308,   314,    178,  488, 

494. 
Retinitis  leukemica,  352. 
Retinitis  of  Blight's  disease,  107. 
Retroperitoneal  echinococci,  512. 
Rhabditis,  varieties  of,  544. 
Rheumatism,  144. 

acute,  sweats  of,  478. 

acute  articular,  2  1  1,  252. 
with  atypical  course,    178. 

articular,  in  a  chorus  girl,  2  1s. 

chronic,  2  t  1. 

Rheumatism,  chronic  articular,  2  13,  246 
etiology  of,  243. 

joint  implication  in,  2  1  1. 

pathology  of,  2  is. 

treatmenl  of.  257. 
combination  of,  with  gout,  1  Is. 
gonorrheal,  175. 
internal  treatment  of,  _'.".7. 
occurrence  of,  in  hemophiliacs,  113,  116. 
pseudo-articular,  256. 
secondary  chronic,  244. 
simulation  ni,  by  trichinosis,  559. 
Rheumatisme    articulaire    chronique    pro- 
gressdf,  244. 

(Informant .  244. 

goutteux,  'hat hesique,  244. 


Rheumatisme  infectieux,  244. 

noueux,  211. 
Rheumatoid,  acute,  256. 

tuberculous,  256. 
Rhinagra,  1  13. 

Rickets  and  enlarged  spleen,  384. 
Robin's  obesity  cure,  1G4. 
Roborants  in  Bodgkin's  disease,  381. 
Roborat,  48,  70,  169. 

Romanowsky  stains,  292,  296,  299,  307,  346. 
Röntgen  rays.     See  X-rays. 
Rovsing,  views  of,  on  unilateral  hematuria, 

447. 
Rowing,  72. 
Rubner's  calculations  in  metabolism,  9. 

calorimetric  investigations,  5. 

law  of  the  conservation  of  energy,  2. 

law  of  the  development  of  tlie  surface,  5 


Salicylic  acid  poisoning,  503. 
Salines  in  hemophilia.    153. 
Saliva,  increased  in  scurvy.   103. 

Salkowski's  case  of  pentosuria,  263. 

discovery  of  pentosuria,  267. 
Sanatoria,  dietetics  in,  71. 

influence  of  life  in.  (17. 

treatmenl  of  chlorosis  in,  339. 
Sand-flea,  disease  caused  by,  ">72. 
Santonin  for  expulsion  of  parasites,  550. 

for  oxyuriasis,  552 
Sarcomata,  239. 

multiple. 
Sarcopsylla  penetrans.  572. 
SarCOpteS  hominis,  501. 

scabiei,  Linne,  566. 
Saturnine  poisoning.    See  Lead. 
Sausage  poisoning,  601 . 

Scabies,  diagnosis  and  treatment  of.  568. 

Scarlatina  followed  by  purpura.    182. 

Scharbock 

Sciatic.i  in  diabetes  insipidus.   1  1  1. 
Schmaltz.'-  pycnoinef  cr.  28  I. 

Schmaltz's  teal   for  specific  gravity 

blood,  284. 
Schmidt 's  fermentation  test ,  15. 
Schmidt's  tesl  did,  is. 
Schön  lei  n's  disease,  173. 
Scleroderma,  213. 


644 


INDEX 


Scrotum,  eehinococci  of,  544. 

excessive  development  of,  151. 
Scurvy,  388,  485. 

absence  of,   in  Nansen  Expedition,  393, 
412. 

American  Collective  Report  on,  393,  404, 
485. 

as  an  infectious  disease,  399. 

bacillus  found  in,  394. 

constitutional  phenomena  of,  402. 

contraction  of,  by  nurses,  395. 

diagnosis  of,  409. 

etiology  of,  393. 

experimental  study  of,  393. 

external  signs  of,  402,  409. 

fatal  outcome  of,  410. 

faulty  nutrition,  a  cause  of,  397. 

frequency  of,  in  Alaska,  392. 

geographic  distribution  of,  391. 

general  and  special  treatment  of,  413. 

gums  the  chief  seat  of,  402. 

hereditary  predisposition  to,  396. 

Hirsch's  tabulations  of,  391. 

history  of,  388. 

infantile,  393,  395,  400,  404. 

no  known  pathogenic  agent  of,  393. 

occurrence  of,  among  seamen,  411,  412. 
among  Tartars,  395. 
among  the  wealthy,  397. 
among  United  States  troops,  392. 
during  siege  of  Ladysmith,  399. 
during  siege  of  Paris,  397. 
in  antiquity,  389. 
in  Russia,  395. 
in  the  tropics,  392. 

pathological  anatomy  of,  399. 

predisposition  to,  396. 

prevention  of,  in  English  marine,  411. 

production  of,  in  monkeys,  394. 

prognosis  of,  410. 

prophylaxis  of,  395,  410. 

rarity  of  severe  forms  of,  408. 

recovery  from,  408. 

symptomatology  of,  401 . 

treatment  of,  410. 
Sea-baths,  in  anemia,  310. 
Seamen,  scurvy  among,  411. 
Sebaceous  glands,  parasites  in,  570. 
Semilunar  ganglia,  cauterization  of,  219. 

extirpation  of,  219. 
Seneca's  views  of  gout,  147. 
Sensuality  awakened  in  the  young,  332. 


Sepsis,  myxedema  followed  by,  186. 

severe,  hemorrhages  in,  485. 
Septicemia,  conveyed  by  mice,  571. 
Serum  of  the  blood,  285. 
Serum,  specific  gravity  of,  327. 
Servant  girls,  chlorosis  among,  332. 
Sexual  disturbances,  334. 
Sexual  functions  in  chlorosis,  323. 
Sexual  organs,  anomalies  of,  334. 
Siderosis,  314. 

Silbermann's  views  of  purpura,  464. 
Silenus  as  type  of  obesity,  152,  156. 
Siven,  experiments  of,  15. 
Skalotyrbe,   389,  390. 
Skin,  affections  of,  in  gout,  143. 
in  rheumatism,  252. 

bleaching  of,  in  Addison's  disease,  201. 

bronzing  of,  212,  220,  226. 

changes  of,  in  trichinosis,  557. 

condition  of,  in  gouty  attack,  134. 
in  myxedema,  179,  184. 
in  rheumatism,  251. 

discoloration  of,  201. 

doughy  appearance  of,  320. 

edematous  infiltration  of,  320. 

faded-yellow,  in  anemia,  312. 

greenish,  320,  336. 

hemorrhages  of,  464. 

itching  of,  in  diabetes,  85. 

lymphadenoids  in,  375. 

marbling  of,  483. 

metabolism  stimulated  from,  380. 

non-ulcerating  nodes  in,  352. 

pallid,  in  anemia,  320. 

pigmentation  of,  218. 

trophic  processes  of,  194. 

uninjured,  hemorrhage  from,  426. 
Skull,  changes  of,  in  acromegalia,  235. 
Sleepiness  in  chlorosis,  324. 
Smallpox,  hemorrhagic,  484. 
Sodium-biurate,  127. 
Sodium  chlorid  in  diabetic  urine,  112. 
Sodium-quadriurate,  127. 
Sodium  urate,  acid,  127. 
Solar  plexus,  changes  of,  in  Addison's  dis- 
ease, 216. 
Soxhlet  sterilizer,  486. 
Special  sense,  organs  of,  325. 
Spectroscope,  use  of,  287. 
Speech  in  myxedema,  185. 
Spermin,  197. 
Sphacelinic  acid,  poisoning  by,  598. 


INDEX 


645 


Sphacelotoxin,  598. 
Sphygmogenin,  210. 
Spices,  use  of,  in  diabetes,  109. 
Spinal  cord,  changes  of,  in  Addison's  dis- 
ease, 216. 
echinococcus  of,  534. 
Spinal  roots,  neurotic  processes  in,  217. 
Spirilli,  relapsing  fever,  571. 
Splanchnic  nerve,  degeneration  of,  216. 
Splanchnomegalia,  237. 
Spleen,  cold  applications  to,  386. 
echinococcus  of,  541. 
enlargement  of,  350,  356,  370,  376,  383, 
384. 
idiopathic,  385. 
in  anemia,  313. 
in  Hodgkin's  disease,  372. 
in  pseudo-leukemia,  3S2. 
hyperplasia  of,  363,  383. 
lymph-cell  formation  in,  361. 
pappy  softening  of,  488. 
Splenalgia,  324. 
Splenectomy,  3x6. 
in  children,  3S6. 
Splenica,  371. 

Spleno-lymphatica,  371. 

Spondylose  rliizoiinTu |iie,  246. 

Spongiosa,  236. 

Sporozoa,  506. 

Sport,  value  of,  in  obesity,  176. 

Springs,  bromin-containing,  380. 

iodin,  380. 

.-odium  chlorid,  380. 
Sputum,  gangrenous,  ~>'-'<7. 
Staining  process,  of  Ehrlich,  293. 

Stains,  neut  ral,  '■'•  16. 

tnacid,  348. 

universal,  295. 
Starvation,  21. 

cure  of,  161,  162. 

losses  in.   10,  I  I. 

observal ions  in,  i  I. 
Stasis,  circulatory,  352. 

in  disease  of  I  lie  heart ,   Is. 
uric  acid,   132. 

Statistics  <•!  gout,  130. 
Steinbacher's  eure  of  obesity,  17  1. 
Stiffness  of  joints  in  rheumatism,  247. 
Stippling,  basophilic,  300 
Stomach,  affection  of,  from  ur'>ut,  1  lit. 

atony  and  displacement  of,  335. 

carcinoma  of,  -Ho. 


Stomach,  hyperacidity  of,  47. 

lavage  of,  581,  597. 

in  opium  poisoning,  596. 

leukemic  infiltrations  in,  351. 

perforation  of,  581. 

secretory  activity  of,  323. 
Stomatite  ulcereuse,  389. 
Stomatitis,  aphthous  and  ulcerative,  403. 

from  arnica,  598. 

in  children,  403,  404. 
Stomatokak6,  389,  390. 
Stools,  fatty,  46. 

rice-water,  586. 
Strawberry  cure,  147. 
Styptics.  154. 

Substitution  hcrapy,  188,  193. 
Suffocation,  from  glandular  swelling,  373. 
Sugar,  ingestion  of,  78. 

forbidden  in  diabetes,  109. 

presence  of,  in  urine,  44. 

producers  of,  78. 
Suggestion,  as  cause  of  polyuria,  118. 

effect  of,  75. 
Suggillations,   enormous,   in   purpura,   483, 
491. 

scorbutic,  405. 
Suicide  by  phosphorus  poisoning,  584. 
Sulphonal  poisoning,  591,  592. 
Sulphur,  poisoning,  586. 
Sulphuric  acid,  in  morbus  maculosus,  197. 
Sun  baths  of  ( Selsus,  175. 

Sunstroke,    a    cause    of    diabetes    insipidus, 
119. 

Suprarenals.     See  also  Adrenals. 

Suprarenal  extract,  action  of,  208. 
on  central  nervous  system,  208. 
in  animals,   22  I. 

vaso-constricting  action  of,  208. 

Suprarenin,    210. 

Surface,  law  of  development  of.  -V 
Surgery,  danger  of,  in  bleeders,  152. 
Sweat ,  exhaustive,  178. 
reactive  outbreak  of,  341. 

Sweat    apparatus,    258. 
Sweat   baths,  311. 

in  diabetes,  123. 

Snc.ii    formation,    1  1.3. 
Sweat ing,  '-".'. 

plofuse.     I  I. 

in  leukemia.  3 

Sweetbreads,  forbidden  in  diabetes,  99. 
Switzerland,  prevalence  of  goiter  in.  190, 


646 


INDEX 


Sydenham's  views  of  gout,  147. 
Sympathetic  system,  diseases  of,  216,  218. 

disorders  of,  324. 

neuritic  disease  of,  216. 
Symptom-complex  of  gout,  132. 
Syncope,  in  chlorosis,  324. 
Synovial  fluid,  non-purulent  in  rheumatism, 

249. 
Syphilis,  association  of,  with  gout,  145,  148. 

cerebral,  122. 

diabetes  as  caused  by,  120. 

enlarged  spleen  in,  384. 

hereditary,  384. 

joint  implication  in,  145. 

of  brain,  115. 

over-nutrition  in,  63. 

tertiary,  63. 
Systolic  murmurs,  321. 
Systolic  thrill,  321. 


Tabes  mesenterica,  47. 

Table,  comparative,  of  various  diet  schemes, 
72. 
of  alcohol  and  carbohydrates  in  beer,  106. 
of  carbohydrates  in  fruits,  105. 

in  wines  and  spirits,  106. 
of  Dapper's  diet  scheme,  73. 
of  energy  metabolism  per  square  meter 

of  body  surface,  5. 
of  fatty  foods  and  varieties  of  milk,  104. 
of  food  values  necessary  for  maintenance 

of  N-equilibrium,  14. 
of  percentage  of  carbohydrates  in  bread, 
flour,  vegetables,  104. 
of  fat  in  cheese,  104. 
in  eggs,  104. 
in  meat,  103. 

in  sausages  and  preserved  meats,  104. 
of  rest  values  in  different  diseases,  27. 
Tallqvist  scale,  277. 

Tamburini's  views  of  acromegalia,  241. 
Tannin,  in  diabetes,  123. 
Tape-worm,  514. 

anemia  as  caused  by,  318. 
food  causing  passage  of,  523. 
presence  of,  without  symptoms,  522. 
reflex  symptoms  caused  by,  523. 
removal  of,  525,  526. 
Tape-worm  disease,  prognosis  of,  524. 
therapy  of,  525. 


Tarantula,  bite  of,  575. 

Taste,  anomalies  of,  325. 

Technic  of  over-nutrition  and  under-nutri- 

tion,  69. 
Teeth,  extraction  of,  in  bleeders,  452,  454. 

loosening  of,  140,  485. 
in  scurvy,  403. 

tartar  of,  containing  amebse,  505. 
Temperament,  phlegmatic  in  the  obese,  159. 
Temperature  in  diabetes  insipidus,  114. 

in  myxedema,  185. 

in  scurvy,  407. 

in  trichinosis,  556. 
Tendon  sheaths,  nodules  of,  251. 
Tendons,  stretching  of,  146. 
Tenia  africana,  v.  Linstow,  518. 

asiatica,  v.  Linstow,  518. 

confusa,  Ward,  517. 

crassicollis,  517. 

cucumerina,  Bloch,  516. 

echinococcus,  526. 

transmitted  by  dog,  529,  530. 

flavopunctata,  Weinland,  516. 

hominis  n.  spr.,  519. 

madagascariensis,  Davaine,  517. 

marginata,  517. 

nana,  v.  Siebold,  516. 

saginata,  501,  514,  515. 

serrata,  517. 

solium,  514. 

characteristics  of,  514. 
prevalence  of,  in  Germany,  502. 
Teniaphobia,  524. 
Tension,  specific  energy  of,  5. 
Tension  energy,  consumption  of,  53. 
Tension  power,  calculation  of,  37. 
Tetanus,  thyreoid  therapy  in,  195. 
Tetronal  poisoning,  591. 
Therapy,  dietetic,  in  anemia,  309. 

of  diabetes,  92. 

physical,  in  anemia,  309. 

suprarenal,  225,  226. 
Thermal  baths,  148. 
Thirst,  as  symptom  of  diabetes,  113. 

endurance  of,  in  obesity,  170. 

methods  to  relieve,  118. 
Thirst  cure,  174. 

Thoma-Zeiss  apparatus,  281,  283. 
Thoracic  organs,  lymphadenoids  in,  375. 
Thread-worms,  544. 

Thrombophlebitis    suppurativa     of    pelvic 
veins,  478. 


INDEX 


647 


Thrombosis,  as  cause  of  purpura,  462,  463, 

464,  465. 
Thumb,  exemption  of,  in  rheumatism,  245. 
Thymus  gland  in  acromegalia,  238. 

of  hemophiliacs,  431. 
Thymus  preparations,  193. 
Thyraden,  190. 
Thyreo-antitoxin,  189. 
Thyreoglobulin,  189. 
Thyreoid  cure  of  mental  diseases,  195. 
Thyreoid  extract  in  myxedema,  180. 
Thyreoid  gland,  absence  of,  184. 

administration  of,  29. 

atrophy  of,  188. 

degeneration  of,  180. 

echinococcus  of,  536. 

enlargement  of,  in  acromegalia,  232,  238. 

grafting  of,  187. 

internal  secretory  activity  of,  334. 

iodin  contents  of,  190. 

strumous  degeneration  of,  186. 
Thyreoid  therapy,  188,  191. 

toxic  action  of,  191. 
Thyreoidectomy,  187. 

in  animals,  196. 
Thyreoidin  in  obesity,  175,  176. 
Thyreoiodin,  189,  193. 

as  cure  for  obesity,  194. 

lor  skin  affections,  194. 
Thyreoidiam,  189,  192. 
Ticks,  566. 
Tissue,  consumption  of,  in  diabetes,  90. 

intoxication  necrosis  of,  40. 
Tissue-building  substance,  unknown,  19. 
Tissue  changes  in  myxedema,  185. 
Tissue  decomposition  in  diabetes,  91. 
Tissue  destruction,  39. 
Tissue  hunger,  80. 
Tissue  irritation  in  gout,  1  13. 
Tissue  necrosis  in  goul .  133. 

in  scurvy,    100. 
Tissue  regeneration,  •"»<>. 
Tissues,  parablastic,  1 18. 
Titration  method  of  Liebig,  I. 
Toad-stool  poisoning,  599. 

Tobacco  | >. .i-4 .nil ilt.  595. 

Toe,  uront  in,  136. 

Tongue,  condition  of.  in  Addison's  disease, 
201. 

enlargement  of,  in  acromegalia,  236. 

hyperplasia  of,  236. 

inky  stain  "I.  201. 


Tongue,  muscular  degeneration  of,  236. 
Tonics  in  rheumatism,  257. 
Tophi,  gouty,  135,  137,  138,  146. 

in  burs»  mucosae,  137. 
Toxemia  from  presence  of  parasites,  523. 
Tracheo-bronchial    lymph-glands,    swelling 

of,  351. 
Tracheo-bronchial   mucous   membrane,   in- 
flammation of,  377. 
Tracheotomy  in  opium  poisoning,  596. 
Training,  athletic,  161. 

physical  and  mental,  331. 
Transmission,  pre-natal,  of  relapsing  fever, 

429. 
Transactions  XUIth  International  Medical 

Congress,  126,  127. 
Transudates,  effect  of,  in  metabolism,  44. 
Transvaal,  distoma  infection  in,  513. 
Trauma,  as  cause  of  diabetes,  115,  119. 
Triacid  solution  for  blood  staining,  295. 
Trichina  spiralis,  553. 
Trichina?,  development  of,  554. 

in  pork,  553. 
Trichinosis,  autopsy  reports  of,  55S. 

distribution  of,  553. 

epidemics  of,  555. 

fever  in,  ."»."»»',. 

mortality  of,  558. 

muscle  lameness  in.  556. 

origin  of,  553,  554. 

prognosis  of,  559. 

prophylaxis  of,  559. 

symptoms  of.  556. 

t  real  inent   of.  559. 

Trichocephalus  dispar,  Rudolphi,  0  1s-.  552. 

diagnosis  of.  553. 
Trichomonas,  hominis,  507. 

vaginalis,  I  tonne,  507. 
Trional  poisoning,  .v.M.  592. 
Trombidium  bolosericum,  .">•"■">. 
Trommel's  test,  77,  78,  262. 
Trophic  tracts  in  Addison's  disease,  213. 
Trophoneurosis,  1  12. 

general,  221 . 
Trophoneuroses,  infections,  256. 
Tropon,  18,  7<). 
Tsetse  By  disease,  ">7 1 . 
Tubercular  adenit  is,  376. 
Tuberculoid,  rheumatic,  256. 

Tuberculosis,  adrenal,  21'.». 

chronic,  202. 

destruction  of  adrenals  in,  220. 


648 


INDEX 


Tuberculosis,  intestinal,  47. 

mistaken  for  malaria,  293. 

of  glands,  375. 

pulmonary,  31,  63,  337. 

value  of  increased  nutrition  in,  60,  63. 
Tumor,  hypophysial,  239. 

solid,  537. 

splenic,  direction  of  growth  of,  350. 
Tumors  in  Hodgkin's  disease,  372. 
Tunica  vaginalis,  echinococcus  of,  544. 
Türck's  method  of  blood  counting,  282. 
Turpentinglycuronic  acid,  264. 
Typhoid  bacilli,  291. 
Tyroglyphides,  varieties  of,  566. 


U 
Ulcers,  gouty,  137. 

of  scurvy,  405. 
Uncinariasis,  560. 
Under-nutrition,  54,  67. 

consequences  of,  59. 

employment  of,  for  the  obese,  67. 

in  diabetes,  91. 

indications  for,  62. 

occurrence  of,  59. 

prolonged,  38. 

systematic,  59. 

technic  of,  69. 

when  obesity  is  complicated  by  other  dis- 
eases, 69. 
Urates,  137. 

monosodium,  137. 
Uratica,  125. 
Urea  as  measure  of  metabolism,  4. 

excretion  of,  42. 

in  diabetic  urine,  112. 

in  leukemia,  353. 
Urethra,  distoma  infection  through,  513. 
Uric  acid  as  cause  of  gout,  126. 
Uric  acid,  deposit  of,  25.5. 

condition  of,  in  diabetic  urine,  112. 
in  Hodgkin's  disease,  375. 
in  leukemia,  127. 

excretion  of,  131,  136. 

in  tissues,  127. 

percentage  of,  in  gout,  137. 
Uric  acid  engorgement,  149. 
Uricemia,  128. 
Urina  spastica,  117,  119. 
Urinary  organs,  condition  of,  in  gout,  141, 
142. 


Urinary  products,  44. 

Urination,  painful,  from  parasitic  cause,  560. 

Urine,  changes  in,  in  obesity,  157. 

condition  of,  in  diabetes,  84. 
in  diabetes  insipidus,  64. 
in  hemophilia,  426. 
in  leukemia,  353. 
in  myxedema,  185. 
in  nephritis,  41. 

decrease  of,  in  fevers,  112. 

dextro-rotary,  268. 

elementary  analysis  of,  4. 

estimation  of  excretion  of,  6. 

glycose  in,  269. 

increased  excretion  of,  110. 

morning  flood  of,  112. 

of  herbivora,  264. 

optically  inactive,  270. 

parasites  in,  507. 

pentose  in,  262. 

reducing  substances  in,  269,  270. 

sugar  in,  in  diabetes,  84. 
Urohematoporphyrin,  212. 
Urology,  Fourth  French  Congress  of,  448. 
Urotropin  in  gout,  148. 
Urticaria,  42,  143. 

following  echinococcus  of  liver,  531. 
Uterus,  echinococcus  of,  543. 


Vaccination  of  hemophiliacs,  434,  452. 

Vagina,  papilloma  of,  513. 

Vagrant's  disease,  203. 

Valerian,  in  diabetes,  122,  123. 

"Value"  in  blood  counting,  283. 

Value-estimation  of  blood,  283. 

Valve,  auriculoventricular,  insufficiency  of, 
321. 

Valvular  disease,  uncompensated,  48. 

Vanillin  poisoning,  601. 

Varices  in  the  obese,  69. 

Vascular  apparatus,  capacity  of,  in  hemo- 
philia, 425. 

Vascular  disturbances  of  the  obese,  158. 

Vascular  formation,  deficiency  of,  431. 
retardation  of,  431. 

Vascular  system,  hypoplasia  of,  330. 
imperfect  development  of,  338. 
structure  of,  422,  423. 

Vasomotor  nerves,  anomalous  function  of, 
335. 


INDEX 


649 


Vasomotor  tracts  in  Addison's  disease,  213. 
Vasomotors,  neurosis  of,  336. 
Vegetable  acid  potash,  deficiency  of,  393. 
Vegetable-albumin  preparations,  169. 
Vegetable  poisons,  598. 
Vegetable  potassium,  in  various  foods.  111. 
Vegetables,  fresh,  as  preventive  of  scurvy, 
397. 

in  diet  of  diabetics,  99,  10S,  122,  123. 
of  chlorotics,  341. 

leguminous,  for  the  obese,  170. 
Veins,  of  neck,  swelling  of,  373. 

pelvic.  478. 

spermatic,  478. 
Venesection,  341. 
Venous  thrombosis,  327. 
Vermifuges,  525. 
Vertebra,  chronic  rigidity  of,  248. 
Vertebral    column,    ankylosing    disease    of, 

246. 
Vertigo  in  chlorosis,  •'!_' 1. 

in  gout,  1  13. 
Vesicles  from  filaria,  5  IS. 

miliaria!,  491. 
Vessels,  dwarfed  slate  of,  329. 
Vest ibulum  malorum,  378. 

pharyngis,  378. 
Vibices,  in  scurvy,  404. 

of  purpura,  191. 
Viscera]  complications  in  rheumatism,  251. 
Vitality,  increase  of,  20. 
Voit's  calorimetric  method,  (3,  7. 

experiments,  I. 

I:iw  of  metabolism  and  nutrition,  11,  50. 
Volkmann's  arthritis  deformans,  246. 
Vomiting  <>\  proglottides,  •">_':_>. 
v.  Boesslin  on  obesity,  175. 
v.  Kogerer's  views  of  purpura,  nil. 


W 

Wadd's  \  lew  -  on  corpulence,  163. 
Wasting  diseases,  63,  250. 
Water,  allowance  of,  in  diabetes,  98. 
cold,  in  treatmenl  of  rhe atism,  257. 

demand  "i  I  issues  i<>r,  ;;s. 
excretion  "t,  17. 


Water,  loss  of,  in  blood  and  tissues,  75. 

precautions  in  use  of,  548. 

use  of,  in  the  cure  of  obe>iry,  74. 

value  of,  in  nutrition,  71. 
Water-cress,  infection  conveyed  by,  509. 
Weakness,  sensation  of,  in  anemia,  308. 
Weight,  experimental  demonstrations  of,  4. 

in  regard  to  obesity,  158. 

loss  of,  34. 

in  diabetes,  84. 

normally  heavy,  158. 
Weight  of  body,  maintenance  of,  37. 

significance  of,  38. 
Werlhof's  disease,  457. 
White  blood  corpuscles,  table  of,  299. 
WidaTs  reaction,  290,  21)1. 
Wine  in  dietary  of  diabetics,   100. 
Women,  as  conductors  of  hemophilia,  414. 

diseases  of,  155,  196,  197. 

neuroses  appearing  in,  336. 
Working  cell  substance,  16. 
Worm,  medina,  546. 
Wounds,  fly  larva?  in,  574. 

infection  of,  478. 


X 

X-rays,  burns  from  treatmenl  by,  369,  381. 

examination  by,  of  bleeder's  joint,  132. 

treatmenl  of  leukemia  by,  354,  369. 
Xylose,  267. 


Yeast  fermental ion.  262. 

Youth,  chlorosis  a  disease  "i.  320,  330. 

goul  occurring  in.  L28. 

hemophilia  appearing  in.  1 15. 

life  energy  in.  -U'k 


Ziemann's  stain  327. 

Zipperlein.     See  Gout. 

Zuntz's  researches  in  metabolism,  24. 

Zymoplastio  substance,  12  I. 


ID 


PRACTICAL  DIETETICS. 

WITH  SPECIAL  REFERENCE  TO  DIET  IN  DISEASE. 
By  W.  GILMAN  THOMPSON,  M.D., 

Professor  of  Medicine  in  the  Cornell  Medical  College  of  the  City  of  New  York  ;  Visiting 
Physician  to  the  Presbyterian  and  Bellevue  Hospitals,  New  York. 

LARGE    OCTAVO,    EIGHT    HUNDRED   AND   FOURTEEN 
PAGES,    ILLUSTRATED. 

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''  This  is  at  once  the  best  and  most  exhaustive  book  upon  this  subject  with 
which  we  are  familiar.  The  best  because,  in  the  first  place,  it  is  written  by  a 
teacher  of  therapeutics  who  knows  the  needs  of  the  practicing  physician,  and 
yet  who  has  taught  in  previous  years  as  a  professor  of  physiology  all  that  one 
needs  to  know  in  regard  to  the  principles  of  digestion  and  assimilation.  For 
this  reason  the  author  is  unusually  well  qualified  to  prepare  a  useful  manual,  but 
it  is  not  until  one  has  perused  the  volume  that  he  thoroughly  grasps  the  scope 
and  depth  of  the  manner  in  which  Dr.  Thompson  has  treated  his  subject." 

—  Therapeutic  Gazette. 

"  The  subject  of  the  dietetic  treatment  of  disease  is  not  an  attractive  one. 
This  fact  explains,  no  doubt,  the  comparatively  little  attention  given  it  in  college 
curriculum  and  daily  study.  When  one  proceeds  to  examine  the  valuable  con- 
tributions to  this  subject,  the  scientific  investigations  which  have  been  made  by 
the  United  States  Department  of  Agriculture  at  various  experiment  stations  in 
all  parts  of  the  country,  he  is  convinced  that  it  is  high  time  to  look  into  the 
matter  pretty  thoroughly.  This  book  is  of  value  for  its  summary  of  the  latter 
and  its  application  of  the  knowledge  to  the  treatment  of  the  disease." 

— Brooklyn  Medical  Journal. 

"  The  portion  of  the  work  on  diet  in  the  various  diseases  must  prove  of  much 
value  to  the  practitioner  who  has  sought  in  vain  in  so-called  'practices  of  medi- 
cine'  for  exhaustive  discussion  of  diets  for  special  pathological  conditions.  In 
giving  applicable  diets  few  diseases  are  omitted,  and  the  author  not  only  gives 
his  own  views,  but  quotes  those  of  others,  especially  with  regard  to  such  con- 
ditions as  obesity,  rheumatism,  gout,  and  diabetes,  in  which  proper  feeding  is  of 
such  paramount  importance.     The  volume  contains  nine  full-page  plates." 

—  Medical  Review  of  Renews. 

"  In  the  seven  years  which  have  elapsed  since  the  first  appearance  of  this 
standard  text-bonk  there  have  not  been  the  many  and  important  changes  in 
dietetic  s  that  other  departments  of  our  therapeutics  have  undergone.  Never- 
theless, Dr.  Thompson  has  revised  much  that  was  published  in  the  first  edition, 
and  has  introduced  into  this  one  the  results  of  more  recent  studies  in  Un- 
economic values  of  various  dietaries.  The  general  arrangement  of  the  work  is 
unchanged." — A«w  )  ork  Medical  Journal. 

I ) .     APPLETON      AND     COMPANY,      X  E  W     YORK. 


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APPLETONS' 
MEDICAL  DICTIONARY. 

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nunciation is,  as  a  rule,  indicated  only  by  accenting  the  title  words,  the  derivations  are  given 
briefly,  and  the  French  and  German  equivalents,  and  often  the  Greek,  are  inserted  when  they 
differ  materially  from  the  English.  In  regard  to  orthography,  we  are  glad  to  see  that  Dr. 
Foster  does  not  favor  what  he  calls  the  fad  of  substituting  the  termination  'ic'  for  'ical,'  dis- 
pensing with  the  final  'e'  in  such  terminations  as  'ine'  and  'ide,'  and  suppressing  diphthongs. 
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"  Probably  the  most  complete  and  most  exhaustive  medical  dictionary  in  existence.  We 
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"Although  the  number  of  medical  dictionaries  on  the  market  to-day  is  very  great,  there 
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a  succinct,  clear,  and  accurate  definition." — Solomon  Solis-Cohen,  M.D. 

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DISEASES  OF  THE  HEART 
and  ARTERIAL  SYSTEM 

By  ROBERT  H.  BABCOCK,  A.M.,  M.D. 

Professor  of  Clinical    Medicine   and    Diseases   of  the    Chest,    College    ot    Physicians 

and    Surgeons    (Medical    Department   of    the    Illinois   State    University), 

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"  This  treatise  is  evidently  the  result,  not  only  of  large  clinical  experience,  hut  of 
wide  reading  and  careful  reflection.  The  author  disclaims  any  pretense  of  originality, 
but  it  is  open  to  question  whether  the  conclusions  and  results  of  a  ripe  judgment,  such 
as  are  presented  in  this  volume,  are  not  worth  quite  as  much  as  some  academic  so- 
called  original  work.  Certainly  a  large  amount  of  material,  both  clinical  and  literary, 
has  been  worked  out  and  presented  in  a  most  clear,  succinct,  and  practical  manner. 
The  author's  style  is  pleasing  and  without  ambiguity,  nor  is  the  text  over-loaded  with 
unnecessary  technical  terms.  After  a  careful  perusal  of  Dr.  Babcock's  book  there  are 
two  features  which  strike  the  reader  as  characteristic  and  valuable.  These  are,  on 
the  one  hand,  the  case  histories,  and,  on  the  other,  the  unusual  number  and  value  of 
the  pages  devoted  to  the  therapeutics  of  the  subject.  The  narration  of  cases,  although 
at  times  in  much  detail,  does  not  cause  the  usual  weariness  of  flesh  in  the  reading, 
mainly  because  of  the  interesting  manner  in  which  they  are  written.  They  are 
particularly  well  chosen  to  illustrate  the  manifold  varieties  of  disease  and  the  practical 
wisdom  required  in  the  management  of  actual  cases.  Regarding  the  therapeutic  side 
of  the  work  none  but  words  of  praise  are  required.  So  far  as  the  reviewer's  reading 
goes  there  is  no  more  complete  and  reliable  exposition  of  the  treatment  of  circulatory 
disease  than  that  found  in  this  volume.  That  this  high  commendation  is  deserved  will 
readily  be  admitted  after  reading  chapters  16,  17,  and  18  upon  the  treatment  of  valvular 
heart  disease.  These  chapters  are  distinguished  by  a  fulness  of  detail  and  a  variety  oi 
therapeutic  resource  which  cannot  but  prove  of  great  value,  not  only  to  the  j 
practitioner,  but,  as  well,  to  the  clinician  of  years. 

"The  book  can  be  unhesitatingly  recommended  as  a  distinct  acquisition  to  one's 
working  library." — "Brooklyn  Midical  Journal. 

"  We  commend  to  our  readers  this  work  of  Babcock's  as  a  very  desirable  work 
for  both  the  specialist  and  the  practitioner,  and  wish  the  author  a  most  hearty  wel- 
come for  his  admirable  literary  endeavor." — Medical  News. 

D  .     A  P  P  L  E  T  O  N     AND     COMPANY,    NEW     YORK. 


OBSTETRICS. 

A    TEXT-BOOK  FOR    THE   USE  OF  STUDENTS  AND 
PRACTITIONERS. 

By  J.  WHITRIDGE   WILLIAMS, 

Professor  of  Obstetrics,  Johns  Hopkins  University;  Obstetrician-in-Chief  to  the  Johns 
Hopkins  Hospital;  Gynecologist  to  the  Union  Protestant  Infirmary,  Baltimore,  Md. 

SIX  HUNDRED  AND   THIRTY  ILLUSTRATIONS  IN   THE   TEXT 
AND   EIGHT   COLORED   PLATES. 

Cloth,  $6.00;    Half  Leather,  $6.50. 

SOLD    ONLY    BY    SUBSCRIPTION. 


"The  studies  of  the  anatomy  of  the  uterus  and  its  adnexa  are  unique,  and  afford 
the  student  opportunity  for  attractive  occupation  in  the  acquirement  of  completer 
knowledge.  The  development  of  the  ovum  and  placenta  has  never  been  set  forth  as 
well  in  a  work  on  obstetrics,  according  to  our  view,  as  by  Williams.  The  illustrations 
showing  the  structure  of  the  placenta  are  admirable. 

"  In  the  section  on  obstetric  surgery,  beginning  with  induction  of  abortion  and  ac- 
couchement force,  including  forceps  and  version,  Cesarean  section  and  symphysiotomy, 
destructive  operations,  and  ending  with  operative  procedures  which  do  not  aim  at  a 
delivery,  is  found  quite  the  most  ample  handling  of  operative  obstetrics  that  has  yet 
been  published  in  such  a  treatise.  Here,  again,  illustrations  supplement  the  text  in  an 
instructive  fashion. 

"  Williams's  dealing  with  contracted  and  otherwise  deformed  pelves,  and  the  man- 
agement of  labor  in  such  conditions,  is  most  satisfactory.  Injuries  of  the  birth  canal, 
infection,  hemorrhage,  and  the  puerperium  are  all  prepared  by  one  who  understands  the 
greatest  need  of  the  student,  and  he  tells  him  in  the  fewest  and  plainest  words  possible 
what  he  must  know  to  obtain  success  in  the  practice  of  obstetrics.  It  is  a  book  made 
by  a  clinician,  which  gives  the  most  advanced  exposition  of  the  art  and  is  a  distinct 
addition  to  obstetric  literature. 

"  Much  original  work  has  been  done  in  the  way  of  illustration,  as  well  as  in  the 
preparation  of  the  material  of  many  chapters,  and  the  whole  subject-matter  is  presented 
in  an  original  manner.  The  book  is  a  credit  to  both  author  and  publisher.'' — Buffalo 
Medical  Journal. 

"  At  a  certain  examination  the  question  was  asked:  '  Describe  the  management  of  a 
face  presentation  in  the  M.  D.  P.  position.'  The  examined  men  were  like  '  sheep  before 
the  shearers' — i.  e.,  dumb.  An  investigation  showed  that  the  popular  text-book  made 
scant  reference  to  the  so-called  '  undeliverable  '  position. 

"  Perhaps  a  knowledge  of  this  fact  led  the  reviewer  of  Dr.  Whitridge  Williams's 
work  to  consider,  first,  the  description  of  the  presentation  in  general,  and,  second,  those 
of  the  face  in  particular.  The  admirable  methods  employed  in  explanation  and  the 
ample  demonstrating  drawings  illustrating  these  fundamentals  of  obstetric  knowledge 
show  that  the  author  is  that  rare  combination,  a  teacher  and  a  student  of  students  and 
their  requirements. 

"  Everything  is  detailed  to  the  required  minuteness,  and  beyond  that  nothing.  The 
cuts  and  engravings  are  many,  novel  and  good.  They  fill  a  definite  purpose,  and  that 
purpose  is  not  'padding.'  As  one  reads  page  after  page  the  old-fashioned  words, 
'  Pleasure  and  profit,'  recur  to  the  mind. 

"  It  has  all  the  earmarks  of  success;  it  is  crowded  with  hints  of  practical  value,  and 
it  shows  what  the  trained  hand  and  brain  adopt  as  the  best  methods  in  overcoming  the 
obstacles  of  parturition.  Surely,  if  conscientious  work  and  real  merit  count,  we  may 
expect  to  find  this  volume  upon  the  lists  of  the  colleges  and  treasured  in  private  libra- 
ries."— New  York  State  Journal  of  Medicine. 

D.     APPLETON     AND     COMPANY,     NEW     YORK. 


CHEMICAL  AND  MICROSCOPICAL 
DIAGNOSIS 

By  FRANCIS  CARTER  WOOD,  M.D. 

Adjunct  Professor  of  Clinical  Pathology,  College  of  Physicians  and  Surgeons,  Columbia 
University,  New  York;  Pathologist  to  St.  Luke's  Hospital,  New  York 

With  One  Hundred  and  Eighty-eight  Illustrations  in  the  Text  and 
Nine  Colored  Plates 

8vo.     Cloth,  $5.00  net 

"No  practitioner  of  medicine,  whatever  may  be  his  special 
work,  can  afford  to  be  without  some  book  of  this  sort,  and  the 
present  volume  may  frankly  be  recommended  as  satisfactory." 

— New  York  Medical  Journal. 

"We  regard  this  as  one  of  the  most  important  medical  books 
that  have  appeared  of  late,  and  venture  the  opinion  that  it  will  not 
be  long  before  it  will  be  found  in  the  hands  of  every  laboratory 
worker,  whether  teacher  or  pupil." — Buffalo  Medical  Journal. 

"The  work  at  present  before  us  may  be  unhesitatingly  pro- 
nounced one  of  the  best." — Medical  Review  of  Reviews. 

"  It  is  unnecessary  to  emphasize,  in  the  present  state  of  medical 
knowledge,  the  importance  of  microscopical  and  chemical  exami- 
nations of  the  blood  and  the  secretions  and  excretions  of  the  body 
in  the  diagnosis  of  disease.  Indeed,  this  has  been  so  universally 
appreciated  within  recent  years  that  a  distinct  and  increasing  de- 
mand has  been  created  for  works  of  reference  on  these  and  allied 
subjects.  Several  such  books  already  occupy  honored  positions  in 
this  literature,  and  Dr.  Wood's  book,  the  subject  of  this  review,  is 
the  latest  addition  to  the  library  of  clinical  pathology.  Dr.  Wood's 
book  is  undoubtedly  the  most  complete  book  of  its  kind  that  has 
appeared  in  the  English  language." 

— California  S/a/e  Journal  of  Medicine. 

I).     A  PI»  I.  KT  ON     AND     COMPANY,     NEW     YORK 


THE  DIAGNOSTICS  OF 

INTERNAL  MEDICINE 

A    CLINICAL    TREATISE    UPON    THE   RECOGNIZED    PRINCIPLES    OF 

MEDICAL    DIAGNOSIS,     PREPARED     FOR     THE     USE     OF 

STUDENTS  AND  PRACTITIONERS  OF  MEDICINE 

By  GLENTWORTH  REEVE  BUTLER,  A.  M.,  M.  D. 

Chief  of  the  Second  Medical  Division,  Methodist  Episcopal  Hospital ;  Attending  Physician  to 

the  Brooklyn  Hospital  ;  Consulting  Physician  to  the  Bushwick  Central  Hospital  ;  formerly 

Associate  Physician,  Departments  of  Diseases  of  the  Chest  and  Diseases  of  Children, 

St.    Mary's   Hospital,   Brooklyn,   N.  Y.  ■    Fellow  of   the  New  York  Academy  of 

Medicine;  Member  of  the' Medical  Society  of  the  County  of  Kings,  etc. 

New  Revised  Edition,  Rewritten  and  Enlarged 

224  Illustrations,  Five  Plates,  Twenty-two  Charts.     8vo,  1061  pages 

Cloth,  $6.00 

"  This  is  a  valuable  book  upon  an  important  subject.  The  general  plan  of  the  work,  the 
arrangement  of  subjects,  the  colored  plates,  the  illustrations  and  diagrams,  are  alike  excellent. 
The  book  as  a  whole  is,  consequently,  a  reliable  guide  for  students  and  practitioners  in  this 
very  important  field  of  medical  practice." — Journal  of  Medicine  and  Science. 

"  Works  on  diagnosis  are  comparatively  numerous  at  the  present  time,  but  each  new  one 
has  its  spec'al  features  of  interest  and  value.  The  present  volume  covers  the  greater  portion 
of  the  field  of  internal  medicine  in  a  very  satisfactory  way,  and  undoubtedly  will  be  found  by 
many  more  acceptable  than  other  works.  It  is  particularly  strong  in  its  illustrations  ;  these 
are  generally  very  well  selected  to  illustrate  the  text,  which  itself  is  clear  and  readable.  It  is 
well  worth  a  place  in  the  physician's  library  " — Journal  of  the  American  Medical  Association, 
Chicago. 

"  This  volume  presents  some  unusual  features,  and  will  find  many  readers  who  will  appre- 
ciate the  method  by  which  the  subject  is  treated.  The  great  bulk  of  the  work  deals  with  the 
evidences  of  disease,  and  does  so  in  a  most  satisfactory  manner.  The  student  is  taught  how 
to  proceed  in  the  examination  of  his  patient,  what  routine  questions  are  to  be  asked  such  as 
would  lead  to  a  preliminary  opinion  which  in  turn  would  suggest  certain  examinations  in 
detail.  The  author  teaches  not  only  what  to  do,  but  how  to  do  it,  and  his  advice  and  method 
of  diagnosis  are  to  be  highly  recommended.  The  smaller  details,  which  only  acute  observers 
notice,  are  pointed  out  and  their  significance  is  weighed.  It  will  be  of  service  as  a  reference 
book  in  suggesting  explanations  in  cases  where  but  one  or  few  symptoms,  not  pathognomonic, 
are  presented  for  diagnosis  — for  each  symptom  is  explained  and  the  ordinary  diseases  in  which 
it  occurs  are  mentioned,  while  in  the  latter  part  of  the  book  the  diseases  are  treated  separately, 
so  that  direct  suggestions  can  be  immediately  considered  without  consulting  another  volume. 
All  the  modern  laboratory  methods  are  well  described,  the  chapters  on  the  blood  and  stomach 
contents  being  especially  good,  though  brief.  The  thorough  modernness  of  the  instruction  is 
well  instanced  by  drawings  of  the  culex  and  anopheles  genera  of  mosquitoes.  The  author  is 
evidently  fully  conversant  with  the  clinical  evidences  of  disease,  for  his  treatment  of  the 
chapters  on  the  signs  and  symptoms  which  present  themselves  in  the  patient  is  unusually  well 
balanced  with  reference  to  their  importance.  The  section  on  pain  is  very  thorough  ;  the 
illustrations  are  profuse  and  particularly  instructive."— -Medical  Record. 

D.   APPLETON   AND   COMPANY,   NEW  YORK 


